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外文医学文献导读(三十五):《脂多糖诱导的急性肺损伤/呼吸窘迫综合征专题》
2020-05-29 09:07     (点击: )
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本次专题的检索年限:2018-2020

检索式:

1、(Acute Lung Injury OR ALI) AND (lipopolysaccharides OR LPS )

2(Acute respiratory distress syndrome OR ARDS ) AND (lipopolysaccharides OR LPS )

 

使用的数据库:PubMedFMRS

以下链接无法获取全文,可通过FMRS平台进行“文献请求”或百链云图书馆进行“文献传递”。

 

编号:1

题名:New pre-clinical evidence of anti-inflammatory effect and safety of a substituted fluorophenyl imidazole.

新的临床前证据表明取代氟苯基咪唑的抗炎作用和安全性

作者:Dos Santos Nascimento, MVP;Mattar Munhoz, AC;De Campos Facchin, BM;Fratoni, E;Rossa, TA;Mandolesi Sá, M;Campa, CC;Ciraolo, E;Hirsch, E;Dalmarco, EM

出处:Biomed Pharmacother.2019,111:1399-1407

IF3.743

摘要:  Acute Respiratory Distress Syndrome (ARDS) is an inflammatory condition with high mortality rates, and there is still no pharmacological approach with proven effectiveness. In the past few years, several imidazole small molecules have been developed to treat conditions in which inflammation plays a central role. In the present work, we hypothesize that a novel substituted fluorophenyl imidazole synthetized by our research group would present in vivo anti-inflammatory effect in an ARDS murine model induced by LPS. Results shows that the fluorophenyl imidazole has the ability to inhibit leukocyte migration to the bronchoalveolar lavage fluid and lung tissue of animals challenged intranasally with LPS. Furthermore, this inhibition is followed with reduction in myeloperoxidase activity, nitric oxide metabolites generation and cytokines (TNF-α, IL-6, IL-17, IFN-γ and IL-10) secretion. This effect is at least partly related to the capacity of the fluorophenyl imidazole in inhibit p38 MAPK and NF-κB phosphorylation. Finally, fluorophenyl imidazole showed no signs of acute oral toxicity in the toxicological protocol suggested by OECD 423. Taken together, the results shows that fluorophenyl imidazole is a promising prototype for the development of a novel anti-inflammatory drug in which p38 MAPK and NF-κB plays a pivotal role.

主题词:Anti-Inflammatory Agents/pharmacology*/消炎药/药理学*

主题词:Imidazoles/pharmacology*/咪唑类/药理学*

主题词:Inflammation/drug therapy*/炎症/药物疗法*

主题词:Lipopolysaccharides/pharmacology/脂多糖类/药理学

主题词:Respiratory Distress Syndrome, Adult/呼吸窘迫综合征, 成人

主题词:p38 Mitogen-Activated Protein Kinases/metabolism/p38丝裂原活化蛋白激酶类/代谢

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:2

题名:Metformin relieves acute respiratory distress syndrome by reducing miR-138 expression.

       甲双胍通过减少miR-138表达来缓解急性呼吸窘迫综合

作者:Yu, LL;Zhu, M;Huang, Y;Zhao, YM;Wen, JJ;Yang, XJ;Wu, P

出处:Eur Rev Med Pharmacol Sci.2018,22(16):5355-5363

IF2.721

摘要:  OBJECTIVE:To investigate whether metformin can relieve acute respiratory distress syndrome (ARDS). Its potential mechanism was also explored. MATERIALS AND METHODS:The ARDS model was established by injecting LPS into mice that received metformin in advance and the mice in the control group. Pulmonary edema was detected by W/D ratios (wet-to-dry weight ratios), and the vascular exudation was reflected by the protein content and cell number of alveolar lavage fluid. Meanwhile, MPO (myeloperoxidase) activity assay was performed to analyze the neutrophil aggregation. The expression of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-17, were detected by enzyme-linked immunosorbent assay (ELISA). This series of experiments reflected the alleviation effect of metformin on ARDS. To further study the mechanism, we cultured alveolar macrophages (NR8383) in vitro and treated them with LPS and metformin. Western blot was used to detect the phosphorylation levels of p38, ERK, NF-kB, and SIRT1 expression level. Bioinformatics method was then used to predict the binding of miR-138 to SIRT1. The mRNA and protein expression of SIRT1 was detected in NR8383 cells transfected with miR-138 inhibitor. The dual luciferase gene reporter assay was used to detect the relative luciferase activities of miR-138 and SIRT1. RESULTS:Pulmonary edema, vascular exudation, and neutrophil accumulation were observed in the ARDS model mice, and the levels of inflammatory cytokines including TNF-α, IL-1b, IL-6, and IL-17 were significantly increased. After metformin treatment, these pulmonic damage indicators were found to be partially reversed. At the same time, metformin could significantly reduce LPS-induced death. After NR8383 was treated with metformin and LPS, the expression of SIRT1 was higher than that of LPS treatment alone, but the expression of p-p38, p-ERK, and p-NF-κB was significantly decreased. After the addition of metformin in NR8383 after LPS treatment, the expression level of miR-138-5p was significantly decreased, and miR-138-5p was confirmed to target SIRT1 and regulate its expression. CONCLUSIONS:Metformin could reduce LPS-induced pulmonic injury and increase expression of inflammatory factors. A possible mechanism might be that metformin-induced low expression of mir-138-5p could target SIRT1 to increase its expression and suppress the MAPK pathway, thus alleviating ARDS.

主题词:Bronchoalveolar Lavage Fluid/支气管肺泡灌洗液

主题词:Lipopolysaccharides/pharmacology/脂多糖类/药理学

主题词:Lung Injury/drug therapy*/肺损伤/药物疗法*

主题词:Metformin/pharmacology*/二甲双胍/药理学*

主题词:MicroRNAs/genetics*/RNAs/遗传学*

主题词:NF-kappa B/metabolism/NF-κB/代谢

全文链接:https://www.europeanreview.org/article/15737

 

 

编号:3

题名:Tabersonine attenuates lipopolysaccharide-induced acute lung injury via suppressing TRAF6 ubiquitination.

水甘草碱通过抑制TRAF6泛素化减弱脂多糖诱导的急性肺损伤

作者:Zhang, D;Li, X;Hu, Y;Jiang, H;Wu, Y;Ding, Y;Yu, K;He, H;Xu, J;Sun, L;Qian, F

出处:Biochem Pharmacol.2018,154:183-192

IF4.825

摘要:  Sepsis caused by Gram-negative bacteria is one of major causes for the progression of acute lung injury (ALI) with limited treatment and effective medicines. Tabersonine is an indole alkaloid mainly isolated from Catharanthus roseus, and a potential drug candidate for treatment of cancer and Alzheimer's disease (AD), however, its anti-inflammatory effect has not been revealed. In this study, we reported that tabersonine ameliorated lipopolysaccharides (LPS)-induced ALI in vivo and inhibited LPS-mediated macrophage activation in vitro. By using murine ALI model, we found that tabersonine significantly attenuated LPS-induced pathological injury in the lung. Tabersonine also inhibited LPS-mediated neutrophil infiltration, elevation of MPO activity and the production of TNF-α, IL-6 and IL-1β. Furthermore, tabersonine inhibited LPS-induced the production of pro-inflammatory mediators such as iNOS, NO and cytokines by suppressing NF-κB and p38 MAPK/MK2 signaling cascades. Tabersonine reduced the K63-linked polyubiquitination of TRAF6. Taken together, these results suggested that tabersonine has anti-inflammatory activities in vitro and in vivo, and is a potential therapeutic candidate for the treatment of ALI/ARDS.

主题词:Acute Lung Injury/prevention & control*/急性肺损伤/预防与控制*

主题词:Anti-Inflammatory Agents/therapeutic use*/消炎药/治疗应用*

主题词:Indole Alkaloids/therapeutic use*/吲哚生物碱类/治疗应用*

主题词:Lipopolysaccharides/toxicity*/脂多糖类/毒性*

主题词:Quinolines/therapeutic use*/喹啉类/治疗应用*

主题词:TNF Receptor-Associated Factor 6/antagonists & inhibitors*/TNF受体相关因子6/拮抗剂与抑制剂*

主题词:Ubiquitination/drug effects*/遍在蛋白化(作用)/药物作用*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:4

题名:miR-200b/c attenuates lipopolysaccharide-induced early pulmonary fibrosis by targeting ZEB1/2 via p38 MAPK and TGF-β/smad3 signaling pathways.

miR-200b / c通过p38 MAPKTGF-β/ smad3信号通路靶向ZEB1 / 2,减弱脂多糖诱导的早期肺纤维化

作者:Cao, Y;Liu, Y;Ping, F;Yi, L;Zeng, Z;Li, Y

出处:Lab Invest.2018,98(3):339-359

IF3.684

摘要:  Pulmonary fibrosis triggered during the early stage of acute respiratory distress syndrome (ARDS) contributes to poor prognosis in patients. However, whether microRNAs (miRNAs) can serve as therapeutic targets for early pulmonary fibrosis during ARDS is still largely unknown. In this study, we evaluated the effects and mechanisms of miR-200s and its targets ZEB1/2 in lung tissue. An early pulmonary fibrosis mouse model caused by ARDS was established via a lipopolysaccharide (LPS) three-hit regimen. Lentiviral packaged miR-200b/c cDNA or ZEB1/2 shRNA was intratracheally administered into the lungs of C57BL/6 mice 1 day before an LPS injection was administered. In vitro, following a 30-min pretreatment with miR-200b/c or SB203580/SIS3, RLE-6TN cells were stimulated by LPS or LPS + transforming growth factor-β (TGF-β) for 24?h. miR-200b/c and E-cadherin protein expression declined, whereas ZEB1/2 mRNA and protein and vimentin and α-smooth muscle actin (α-SMA) protein levels gradually increased during the development of pulmonary fibrosis. Furthermore, both the overexpression of miR-200b/c and the silencing of ZEB1/2 significantly alleviated pulmonary inflammation and fibrosis, reduced vimentin and α-SMA expression, and increased E-cadherin protein levels. In RLE-6TN cells, LPS combined with TGF-β exerts synergistic effects of increasing vimentin and α-SMA protein levels, increasing p38 and smad3 phosphorylation and reducing E-cadherin protein levels, which were reversed by pretreatment with miR-200b/c or SB203580/SIS3. Our findings demonstrate that miR-200b/c was downregulated, whereas ZEB1/2 was upregulated in the development of LPS-induced early pulmonary fibrosis. miR-200b/c exerts a protective effect by targeting ZEB1/2, which may be associated with the inhibition of p38 MAPK and TGF-β /smad3 signaling pathways.

主题词:Lipopolysaccharides/脂多糖类

主题词:MAP Kinase Signaling System*/MAP激酶信号系统*

主题词:MicroRNAs/metabolism*/RNAs/代谢*

主题词:Pulmonary Fibrosis/metabolism*/肺纤维化/代谢*

主题词:Respiratory Distress Syndrome, Adult/complications/呼吸窘迫综合征, 成人/并发症

主题词:Zinc Finger E-box Binding Homeobox 2/metabolism*/锌指E盒绑定同源盒2/代谢*

主题词:Zinc Finger E-box-Binding Homeobox 1/metabolism*/锌指e-box-binding同源框1/代谢*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:5

题名:New thiazolidinedione LPSF/GQ-2 inhibits NFκB and MAPK activation in LPS-induced acute lung inflammation.

新噻唑烷二酮LPSF / GQ-2抑制LPS诱导的急性肺部炎症中的NFκBMAPK活化

作者:Santos, LAMD;Rodrigues, GB;Mota, FVB;França, MER;de Souza Barbosa, KP;Oliveira, WH;Rocha, SWS;Lós, DB;Silva, AKS;Silva, TGD;Peixoto, CA

出处:Int Immunopharmacol.2018,57:91-101

IF3.361

摘要:  Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are responsible for high mortality rates in critical patients. Despite >50years of intensive research, there is no pharmacologically effective treatment to treat ALI. PPARs agonists, chemically named thiazolidinediones (TZDs) have emerged as potential drugs for the treatment of ALI and ARDS due to their anti-inflammatory efficacy. The present study aims to evaluate the potential anti-inflammatory effects of new TZDs derivatives, LPSF/GQ-2 and LPSF/RA-4, on ALI induced by LPS. BALB/c mice were divided into five groups: 1) Control; 2) LPS intranasal 25μg; 3) LPSF/GQ-2 30mg/kg+LPS; 4) LPSF/RA-4 20mg/kg+LPS; and 5) DEXA 1mg/Kg+LPS. BALF analyses revealed that LPSF/GQ-2 and LPSF/RA-4 reduced NO levels in BALF and inflammatory cell infiltration induced by LPS. MPO levels were also reduced by the LPSF/GQ-2 and LPSF/RA-4 pre-treatments. In contrast, histopathological analyses showed better tissue protection with LPSF/GQ-2 than DEXA and LPSF/RA-4 groups. Similarly, LPSF/GQ-2 reduced inflammatory markers (IL-1, iNOS, TNFα, IL-1β, IL-6) better than LPSF/RA-4. The LPSF/GQ-2 anti-inflammatory action could be attributed to the inhibition of NFκB, ERK, p38, and PARP pathways. In contrast, LPSF/RA-4 had no effect on the expression of p38, JNK, NFκB. The present study indicates that LPSF/GQ-2 presents a potential therapeutic role as an anti-inflammatory drug for ALI.

主题词:Acute Lung Injury/drug therapy*/急性肺损伤/药物疗法*

主题词:Anti-Inflammatory Agents/therapeutic use*/消炎药/治疗应用*

主题词:Lipopolysaccharides/immunology/脂多糖类/免疫学

主题词:NF-kappa B/metabolism*/NF-κB/代谢*

主题词:Pneumonia/drug therapy*/肺炎/药物疗法*

主题词:Respiratory Distress Syndrome, Adult/drug therapy*/呼吸窘迫综合征, 成人/药物疗法*

主题词:Thiazolidinediones/therapeutic use*/噻唑烷二酮类/治疗应用*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:6

题名:Apigenin C-glycosides of Microcos paniculata protects lipopolysaccharide induced apoptosis and inflammation in acute lung injury through TLR4 signaling pathway.

破布叶的芹菜素C-糖苷通过TLR4信号通路保护脂多糖诱导的急性肺损伤中的细胞凋亡和炎症

作者:Li, K;He, Z;Wang, X;Pineda, M;Chen, R;Liu, H;Ma, K;Shen, H;Wu, C;Huang, N;Pan, T;Liu, Y;Guo, J

出处:Free Radic Biol Med.2018,124:163-175

IF5.657

摘要:  Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are life-threatening conditions with high morbility and mortality, underscoring the urgent need for novel treatments. Leaves of the medicinal herb Microcos paniculata have been traditionally used for treating upper airway infections, by virtue of its content of flavonoids such as apigenin C-glycosides (ACGs). C-glycosides have been shown to exert strong anti-inflammatory properties, although their mechanism of action remains unknown. Herein, hypothesizing that ACGs from M. paniculata inhibit progression of ALI, we used the experimental model of lipopolysaccharide (LPS)-induced ALI in BALB/c mice to evaluate the therapeutic potential of purified ACGs. Our results showed that M. paniculata ACGs inhibited lung inflammation in animals undergoing ALI. The protective effects of ACGs were assessed by determination of cytokine levels and in situ analysis of lung inflammation. ACGs reduced the pulmonary edema and microvascular permeability, demonstrating a dose-dependent down-regulation of LPS-induced TNF-α, IL-6 and IL-1β expression in lung tissue and bronchoalveolar lavage fluid, along with reduced apoptosis. Moreover, metabolic profiling of mice serum and subsequent Ingenuity Pathway Analysis suggested that ACGs activated protective protein networks and pathways involving inflammatory regulators and apoptosis-related factors, such as JNK, ERK1/2 and caspase-3/7, suggesting that ACGs-dependent effects were related to MAPKs and mitochondrial apoptosis pathways. These results were further supported by evaluation of protein expression, showing that ACGs blocked LPS-activated phosphorylation of p38, ERK1/2 and JNK on the MAPKs signaling, and significantly upregulated the expression of Bcl-2 whilst down-regulated Bax and cleaved caspase-3. Remarkably, ACGs inhibited the LPS-dependent TLR4 and TRPC6 upregulation observed during ALI. Our study shows for the first time that ACGs inhibit acute inflammation and apoptosis by suppressing activation of TLR4/TRPC6 signaling pathway in a murine model of ALI. Our findings provide new evidence for better understanding the anti-inflammatory effects of ACGs. In this regard, ACGs could be exploited in the development of novel therapeutics for ALI and ARDS.

主题词:Acute Lung Injury/prevention & control*/急性肺损伤/预防与控制*

主题词:Apigenin/pharmacology*/芹菜素/药理学*

主题词:Apoptosis/drug effects*/细胞凋亡/药物作用*

主题词:Lipopolysaccharides/toxicity*/脂多糖类/毒性*

主题词:Malvaceae/chemistry*/锦葵科/化学*

主题词:Pneumonia/prevention & control*/肺炎/预防与控制*

主题词:Protective Agents/pharmacology*/预防和防护用药/药理学*

主题词:Toll-Like Receptor 4/metabolism*/Toll样受体4/代谢*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:7

题名:AIBP augments cholesterol efflux from alveolar macrophages to surfactant and reduces acute lung inflammation.

AIBP增加胆固醇从肺泡巨噬细胞外流到表面活性物质并减少急性肺部炎症

作者:Choi, SH;Wallace, AM;Schneider, DA;Burg, E;Kim, J;Alekseeva, E;Ubags, ND;Cool, CD;Fang, L;Suratt, BT;Miller, YI

出处:JCI Insight.2018,3(16):

IF6.014

摘要:  Acute respiratory distress syndrome (ARDS) is characterized by an excessive pulmonary inflammatory response. Removal of excess cholesterol from the plasma membrane of inflammatory cells helps reduce their activation. The secreted apolipoprotein A-I binding protein (AIBP) has been shown to augment cholesterol efflux from endothelial cells to the plasma lipoprotein HDL. Here, we find that AIBP was expressed in inflammatory cells in the human lung and was secreted into the bronchoalveolar space in mice subjected to inhalation of LPS. AIBP bound surfactant protein B and increased cholesterol efflux from alveolar macrophages to calfactant, a therapeutic surfactant formulation. In vitro, AIBP in the presence of surfactant reduced LPS-induced p65, ERK1/2 and p38 phosphorylation, and IL-6 secretion by alveolar macrophages. In vivo, inhalation of AIBP significantly reduced LPS-induced airspace neutrophilia, alveolar capillary leak, and secretion of IL-6. These results suggest that, similar to HDL in plasma, surfactant serves as a cholesterol acceptor in the lung. Furthermore, lung injury increases pulmonary AIBP expression, which likely serves to promote cholesterol efflux to surfactant and reduce inflammation.

主题词:Apolipoprotein A-I/metabolism*/载脂蛋白A-Ⅰ/代谢*

主题词:Lipopolysaccharides/immunology/脂多糖类/免疫学

主题词:Macrophages, Alveolar/immunology*/巨噬细胞, 肺泡/免疫学*

主题词:Pneumonia, Bacterial/immunology*/肺炎, 细菌性/免疫学*

主题词:Racemases and Epimerases/metabolism*/消旋酶类和差向异构酶类/代谢*

主题词:Recombinant Proteins/immunology/重组蛋白质类/免疫学

主题词:Respiratory Distress Syndrome, Adult/immunology*/呼吸窘迫综合征, 成人/免疫学*

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141166/

 

 

编号:8

题名:Nur77 limits endothelial barrier disruption to LPS in the mouse lung.

Nur77限制小鼠肺中LPS的内皮屏障破坏

作者:Zhu, N;Zhang, GX;Yi, B;Guo, ZF;Jang, S;Yin, Y;Yang, F;Summer, R;Sun, J

出处:Am J Physiol Lung Cell Mol Physiol.2019,317(5):L615-L624

IF4.06

摘要:  Nur77 is an orphan nuclear receptor implicated in the regulation of a wide range of biological processes, including the maintenance of systemic blood vessel homeostasis. Although Nur77 is known to be expressed in the lung, its role in regulating pulmonary vascular functions remains entirely unknown. In this study, we found that Nur77 is expressed at high levels in the lung, and its expression is markedly upregulated in response to LPS administration. While the pulmonary vasculature of mice that lacked Nur77 appeared to function normally under homeostatic conditions, we observed a dramatic decrease in its barrier functions after exposure to LPS, as demonstrated by an increase in serum proteins in the bronchoalveolar lavage fluid and a reduction in the expression of endothelial junctional proteins, such as vascular endothelial cadherin (VE-cadherin) and β-catenin. Similarly, we found that siRNA knockdown of Nur77 in lung microvascular endothelial cells also reduced VE-cadherin and β-catenin expression and increased the quantity of fluorescein isothiocyanate-labeled dextran transporting across LPS-injured endothelial monolayers. Consistent with Nur77 playing a vascular protective role, we found that adenoviral-mediated overexpression of Nur77 both enhanced expression of VE-cadherin and β-catenin and augmented endothelial barrier protection to LPS in cultured cells. Mechanistically, Nur77 appeared to mediate its protective effects, at least in part, by binding to β-catenin and preventing its degradation. Our findings demonstrate a key role for Nur77 in the maintenance of lung endothelial barrier protection to LPS and suggest that therapeutic strategies aimed at augmenting Nur77 levels might be effective in treating a wide variety of inflammatory vascular diseases of the lung.

主题词:Acute Lung Injury/complications*/急性肺损伤/并发症*

主题词:Capillary Permeability/drug effects*/毛细血管通透性/药物作用*

主题词:Endothelial Cells/drug effects*/内皮细胞/药物作用*

主题词:Lipopolysaccharides/adverse effects*/脂多糖类/副作用*

主题词:Nuclear Receptor Subfamily 4, Group A, Member 1/physiology*/细胞核受体,亚科4A组,成员1/生理学*

主题词:Pneumonia/prevention & control*/肺炎/预防与控制*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:9

题名:Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing Polarization of M2 Subtype Macrophages.

钙网蛋白阻断剂通过诱导M2亚型巨噬细胞极化来减轻小鼠急性肺损伤

作者:Jiang, Z;Chen, Z;Hu, L;Qiu, L;Zhu, L

出处:Front Immunol.2020,11:11

IF4.716

摘要:  Calreticulin (CALR) has anti-tumor effects by increasing dendritic cell maturation and tumor antigen presentation. However, whether CALR affects macrophages and modulates progression of acute respiratory distress syndrome/acute lung injury (ARDS/ALI) remains unknown. In this study, we discovered that CALR protein was highly expressed in the mice with LPS-induced ALI and CALR expression level was positively correlated to the severity of ALI. Commercial anti-CALR antibody (aCALR) can neutralize recombinant CALR (rCALR) and suppress the expression of TNF-alpha and IL-6 in the rCALR-treated macrophages. Blocking CALR activity by intraperitoneal (i.p.) administration of aCALR significantly suppressed ALI, accompanied with lower total cell counts, neutrophil and T cell infiltration in bronchoalveolar lavage (BAL) and lung tissues. The expression of CXCL15, IL-6, IL-1beta, TNF-alpha, and CALR were significantly reduced, in association with more polarization of Siglec F+CD206+M2 subtype macrophages in the aCALR-treated mice. Pre-depletion of circulating monocytes did not abolish the aCALR-mediated suppression of ALI. Further analysis in bone marrow-derived macrophages (BMDMs) showed that aCALR suppressed the expression of CD80, IL-6, IL-1beta, IL-18, NLRP3, and p-p38 MAPK; but enhanced the expression of CD206 and IL-10. In addition, we observed more expression and phosphorylation of STAT6 in the aCALR-treated BMDM. Lack of STAT6 resulted in comparable and slightly higher expression of CALR, TNF-alpha and IL-6 in the aCALR-treated STAT6-/- BMDMs than the untreated cells. Therefore, we conclude that CALR is a novel biomarker in the evaluation of ALI. Blocking CALR activity by aCALR effectively suppressed ALI independent of circulating monocytes. Siglec F+CD206+M2 subtype macrophages and p38 MAPK/STAT6 signaling pathway played important role in the immune regulation of aCALR. Blocking CALR activity is a promising therapeutic approach in the treatment of ARDS/ALI.

关键词acute lung injury (ALI) ; anti-calreticulin antibody (aCALR) ; calreticulin (CALR) ; cytokines ; macrophages

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002388/

 

 

编号:10

题名:Dapk1 improves inflammation, oxidative stress and autophagy in LPS-induced acute lung injury via p38MAPK/NF-κB signaling pathway.

Dapk1通过p38MAPK /NF-κB信号通路改善LPS诱导的急性肺损伤中的炎症,氧化应激和自噬

作者:Li, T;Wu, YN;Wang, H;Ma, JY;Zhai, SS;Duan, J

出处:Mol Immunol.2020,120:13-22

IF3.064

摘要:  OBJECTIVE:To investigate the impact of death-associated protein kinase 1 (Dapk1) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) via p38MAPK/NF-κB pathway. METHODS:Dapk1+/+ and Dapk1-/- mice were randomized into Control, LPS, SB203580 (a p38MAPK pathway inhibitor) + LPS, and PDTC (a NF-κB pathway inhibitor) + LPS groups. Cell counts, lung wet to dry weight ratio (W/D weight ratio), as well as indicators of oxidative stress were determined followed by the detection with HE staining, ELISA, qRT-PCR, Western blotting and Immunofluorescence. Besides, to explore whether the effect of Dapk1 on ALI directly mediated via p38MAPK/NF-κB pathway, mice were injected with TC-DAPK 6 (a Dapk1 inhibitor) with or without SB203580/PDTC before LPS administration. RESULTS:LPS induced lung injury with increased lung W/D weight ratio, which could be partly reversed by SB203580 and PDTC in LPS-induced mice with activated p38MAPK/NF-κB pathway in lung tissues, especially in Dapk1-/- mice. SB203580 and PDTC reduced total cells and neutrophils in BALF in LPS-induced mice, accompanying with decreased levels of TNF-α, IL-6, MPO, LPO and MDA and the expressions of beclin-1, Atg5 and LC3II, but with the up-regulated activities of SOD and GSH-Px, as well as p62 protein expression. Besides, TC-DAPK 6 aggravated the pathologic injury in LPS-induced ALI with more serious inflammatory response, oxidative stress and autophagy as well as the activated p38MAPK/NF-κB pathway, which were reversed by SB203580 or PDTC. CONCLUSION:Dapk1 improved oxidative stress, inhibited autophagy, and reduce inflammatory response of LPS-induced ALI mice by inhibiting p38MAPK/NF-κB pathway.

主题词:Acute Lung Injury/metabolism*/急性肺损伤/代谢*

主题词:Death-Associated Protein Kinases/metabolism*/死亡相关蛋白激酶/代谢*

主题词:Lipopolysaccharides/toxicity/脂多糖类/毒性

主题词:NF-kappa B/metabolism/NF-κB/代谢

主题词:Pyridines/pharmacology/吡啶类/药理学

主题词:p38 Mitogen-Activated Protein Kinases/metabolism/p38丝裂原活化蛋白激酶类/代谢

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编号:11

题名:Vanillin protects lipopolysaccharide-induced acute lung injury by inhibiting ERK1/2, p38 and NF-κB pathway.

香兰素通过抑制ERK1 / 2p38NF-κB途径来保护脂多糖诱导的急性肺损伤

作者:Guo, T;Su, Z;Wang, Q;Hou, W;Li, J;Zhang, L;Zhang, J

出处:Future Med Chem.2019,11(16):2081-2094

IF3.617

摘要:  Aim: Thus far, the anti-inflammatory effect of vanillin in acute lung injury (ALI) has not been studied. This study aimed to investigate the effect of vanillin in lipopolysaccharide (LPS)-induced ALI. Results & methodology: Our study detected the anti-inflammatory effects of vanillin by ELISA and western blot, respectively. Pretreatment of mice with vanillin significantly attenuated LPS-stimulated lung histopathological changes, myeloperoxidase activity and expression levels of proinflammatory cytokines by inhibiting the phosphorylation activities of ERK1/2, p38, AKT and NF-κB p65. In addition, vanillin inhibited LPS-induced TNF-α and IL-6 expression in RAW264.7 cells via ERK1/2, p38 and NF-κB signaling. Conclusion: Vanillin can inhibit macrophage activation and lung inflammation, which suggests new insights for clinical treatment of ALI.

关键词ALI ; inflammatory diseases ; lipopolysaccharide ; macrophage ; vanillin

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编号:12

题名:Acacia catechu (L.f.) Willd and Scutellaria baicalensis Georgi extracts suppress LPS-induced pro-inflammatory responses through NF-кB, MAPK, and PI3K-Akt signaling pathways in alveolar epithelial type II cells.

和黄芩提取物通过肺泡上皮II型细胞中的NF-кBMAPKPI3K-Akt信号通路抑制LPS诱导的促炎反应

作者:Feng, T;Zhou, L;Gai, S;Zhai, Y;Gou, N;Wang, X;Zhang, X;Cui, M;Wang, L;Wang, S

出处:Phytother Res.2019,33(12):3251-3260

IF3.766

摘要:  Acacia catechu (L.f.) Willd (ACW) and Scutellaria baicalensis Georgi (SBG) are one of the most famous couplet Chinese medicines, widely used for treating infantile cough, phlegm, and fever caused by pulmonary infection. However, the underlying molecular mechanism of their anti-inflammatory activity has not been determined. The aim of this study was to evaluate the protective effect of this couplet Chinese medicines (ACW-SBG) on lipopolysaccharide (LPS)-induced inflammatory responses in acute lung injury (ALI) model of rats and the potential molecular mechanisms responsible for anti-inflammatory activities in alveolar epithelial type II cells (AEC-II). Standardization of the 70% ethanol extract of ACW and SBG was performed by using a validated reversed-phase high-pressure liquid chromatography method. Rats were pretreated with ACW-SBG for 7?days prior to LPS challenge. We assessed the effects of ACW-SBG on the LPS-induced production of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in the bronchoalveolar lavage fluid (BALF). The wet-to-dry weight ratio was calculated, and hematoxylin and eosin staining of lung tissue was performed. Cell viability of AEC-II was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time quantitative reverse transcription polymerase chain reaction assay was carried out to quantify the relative gene expression of TNF-α and IL-1β in AEC-II. The western blotting analysis was executed to elucidate the expression of mediators linked to nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and phosphatidylinositol-3 kinase-protein kinase B (PI3K-Akt) signaling pathways. ACW-SBG significantly decreased lung wet-to-dry weight ratio, ameliorated LPS-induced lung histopathological changes, and reduced the release of inflammatory mediators such as TNF-α and IL-1β in BALF. In AEC-II, we found that the expression of TNF-α mRNA was also inhibited by ACW-SBG. ACW-SBG blocked NF-κB activation by preventing the phosphorylation of NF-κB (p65) as well as the phosphorylation and degradation of the inhibitor of kappa B kinase. ACW-SBG extracts also inhibited the phosphorylation of respective MAPKs (c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38) as well as Akt. The present study demonstrated that ACW-SBG played a potent anti-inflammatory role in LPS-induced ALI in rats. The potential molecular mechanism was involved in attenuating the NF-κB, MAPKs, and PI3K-Akt signaling pathways in LPS-induced AEC-II.

主题词:Acacia/chemistry*/金合欢属/化学*

主题词:Epithelial Cells/metabolism*/上皮细胞/代谢*

主题词:Lipopolysaccharides/therapeutic use*/脂多糖类/治疗应用*

主题词:NF-kappa B/metabolism*/NF-κB/代谢*

主题词:Phosphatidylinositol 3-Kinases/metabolism*/磷脂酰肌醇3-激酶/代谢*

主题词:Plant Extracts/therapeutic use*/植物提取物/治疗应用*

主题词:Proto-Oncogene Proteins c-akt/metabolism*/原癌基因蛋白质c-akt/代谢*

主题词:Scutellaria baicalensis/chemistry*/黄芩/化学*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:13

题名:Novel insights into the role of LRRC8A in ameliorating alveolar fluid clearance in LPS induced acute lung injury.

关于LRRC8A在改善LPS诱导的急性肺损伤肺泡液清除中的作用新见解

作者:Zhang, H;Liu, Y;Li, H;Li, J;Luo, Y;Yan, X

出处:Eur J Pharmacol.2019,861:172613

IF3.17

摘要:  Leucine-rich repeat-containing 8A (LRRC8A) protein was recently identified as an essential component of volume-regulated anion channel which plays a central role in maintaining cell volume. The aim of this study was to elucidate the role of LRRC8A in alveolar fluid clearance (AFC) and the effect of inflammatory cytokines on LRRC8A and the underlying mechanism. Lipopolysaccharide (LPS) was used to generate a rat acute lung injury model. The results showed that the concentrations of IL-1β, TNF-α and IL-6 in bronchoalveolar lavage fluid increased significantly, but the expression of LRRC8A in the lung tissue decreased dramatically in the acute lung injury group followed by a decline in the AFC rate. Additionally, LRRC8A knockdown reduced AFC in normal rats. However, specific overexpression of LRRC8A in the lung could increase AFC. Furthermore, we observed the effects of LPS, IL-1β, TNF-α and IL-6 on the LRRC8A current in alveolar type II (ATII) cells, and IL-1β showed the greatest inhibition among them, which was involved in phospho-p38 activation. Overall, LRRC8A plays an essential role in the progression of AFC in LPS-induced acute lung injury, and chronic treatment with IL-1β or TNF-α could inhibit the function of LRRC8A in ATII cells by targeting phospho-p38. All of the findings suggested that LRRC8A could be a new partner in AFC and a potential target for the treatment of acute lung injury.

主题词:Acute Lung Injury/metabolism*/急性肺损伤/代谢*

主题词:Lipopolysaccharides/pharmacology*/脂多糖类/药理学*

主题词:Membrane Proteins/metabolism*/膜蛋白质类/代谢*

主题词:Pulmonary Alveoli/metabolism*/肺泡/代谢*

主题词:p38 Mitogen-Activated Protein Kinases/metabolism/p38丝裂原活化蛋白激酶类/代谢

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:14

题名:Glycitin alleviates lipopolysaccharide-induced acute lung injury via inhibiting NF-κB and MAPKs pathway activation in mice.

黄豆黄苷通过抑制小鼠中的NF-κBMAPKs途径激活来减轻脂多糖诱导的急性肺损伤

作者:Chen, Y;Guo, S;Jiang, K;Wang, Y;Yang, M;Guo, M

出处:Int Immunopharmacol.2019,75:105749

IF3.361

摘要:  Acute lung injury (ALI) is a pulmonary diffuse dysfunction disease caused by immoderate inflammatory response breaking the coordination of physiological structures and functions, and there are very few effective treatments to reduce high morbidity of ALI in critical patients. Glycitin is a natural ingredient derived from the seeds of leguminous plants and may have potent anti-inflammation features. The purpose of this study was to investigate the anti-inflammation effect of glycitin on LPS-induced ALI in mice and elucidate its possible anti-inflammatory mechanisms. The results of histopathological changes, the wet/dry weight ratio as well as the myeloperoxidase (MPO) activity indicated that glycitin obviously alleviated the lung injury induced by LPS. In addition, qPCR and ELISA results found that glycitin could dose-dependently decrease the expressions of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Western blotting was performed to revealed that glycitin inhibited the activation of NF-κB and MAPKs signaling pathways by suppressing the expression of TLR4 protein and the phosphorylation of IKKβ, IκBα, p65, p38, ERK, and JNK. All data indicated that glycitin could protect lung tissues from LPS-induced inflammation via inhibiting TLR4-mediated NF-κB and MAPKs signaling pathways.

主题词:Acute Lung Injury/drug therapy*/急性肺损伤/药物疗法*

主题词:Anti-Inflammatory Agents/therapeutic use*/消炎药/治疗应用*

主题词:Bronchoalveolar Lavage Fluid/cytology/支气管肺泡灌洗液/细胞学

主题词:Isoflavones/therapeutic use*/异黄酮类/治疗应用*

主题词:Lipopolysaccharides/脂多糖类

主题词:Mitogen-Activated Protein Kinases/antagonists & inhibitors*/丝裂原激活蛋白激酶类/拮抗剂与抑制剂*

主题词:NF-kappa B/antagonists & inhibitors*/NF-κB/拮抗剂与抑制剂*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:15

题名:Bardoxolone treatment alleviates lipopolysaccharide (LPS)-induced acute lung injury through suppressing inflammation and oxidative stress regulated by Nrf2 signaling.

巴多索酮治疗通过抑制由Nrf2信号传导调节的炎症和氧化应激来减轻脂多糖(LPS)诱导的急性肺损伤

作者:Pei, X;Zhang, XJ;Chen, HM

出处:Biochem Biophys Res Commun.2019,516(1):270-277

IF2.705

摘要:  Nuclear factor-erythroid 2 related factor 2 (Nrf2) plays critical roles in attenuating various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Bardoxolone (Bard), a synthetic triterpenoid based on natural product oleanolic acid, is one of the most potent Nrf2 activator. However, if Bard could prevent lipopolysaccharide (LPS)-induced ALI by inducing Nrf2 activation and its down-streaming signals, is still poorly understood. In this study, we attempted to explore the protective effect of Bard on ALI and the underlying molecular mechanisms. The results indicated that Bard significantly attenuated ALI through reducing the lung wet/dry weight ratio and protein concentration, neutrophil infiltration, malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and improving superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, Bard effectively ameliorated histopathological alterations, reactive oxygen species (ROS) production, pro-inflammatory cytokines release, and the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX2) and high mobility group box 1 (HMGB1). Moreover, the inhibitory role of Bard in inflammation was also attributed to its suppression of nuclear factor-κB (NF-κB) signaling. Furthermore, the activation of mitogen-activated protein kinases (MAPKs) signaling, including p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), induced by LPS was substantially ameliorated by Bard. The beneficial effects of Bard on ALI were confirmed in LPS-incubated cells in vitro. Meanwhile, the in vitro studies also demonstrated that Bard-improved ALI was largely due to its role in inducing Nrf2 signaling through a dose-dependent manner. Importantly, we found that Bard-attenuated histological changes, inflammation, ROS production, NF-κB and MAPKs signaling in Nrf2+/+ mice were significantly abolished in mice with Nrf2 knockout. Therefore, our study for the first time provided evidence that Bard could effectively ameliorate LPS-induced ALI by reducing oxidative stress and inflammation mainly through the activation of Nrf2 signaling.

关键词Acute lung injury (ALI) ; Bardoxolone (bard) ; Inflammation ; Nrf2 ; Oxidative stress

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编号:16

题名:CXCL16/CXCR6 is involved in LPS-induced acute lung injury via P38 signalling.

CXCL16 / CXCR6通过P38信号通路参与LPS诱导的急性肺损伤

作者:Tu, GW;Ju, MJ;Zheng, YJ;Hao, GW;Ma, GG;Hou, JY;Zhang, XP;Luo, Z;Lu, LM

出处:J Cell Mol Med.2019,23(8):5380-5389

IF4.658

摘要:  Although several chemokines play key roles in the pathogenesis of acute lung injury (ALI), the roles of chemokine (C-X-C motif) ligand 16 (CXCL16) and its receptor C-X-C chemokine receptor type 6 (CXCR6) in ALI pathogenesis remain to be elucidated. The mRNA and protein expression of CXCL16 and CXCR6 was detected after lipopolysaccharide (LPS) stimulation with or without treatment with the nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC). Lung injury induced by LPS was evaluated in CXCR6 knockout mice. CXCL16 level was elevated in the serum of ALI patients (n=20) compared with healthy controls (n=30). CXCL16 treatment (50, 100, and 200ng/mL) in 16HBE cells significantly decreased the epithelial barrier integrity and E-cadherin expression, and increased CXCR6 expression, reactive oxygen species (ROS) production, and p38 phosphorylation. Knockdown of CXCR6 or treatment with the p38 inhibitor SB203580 abolished the effects of CXCL16. Moreover, treatment of 16HBE cells with LPS (5, 10, 20 and 50μg/mL) significantly increased CXCL16 release as well as the mRNA and protein levels of CXCL16 and CXCR6. The effects of LPS treatment (20μg/mL) were abolished by treatment with PDTC. The results of the luciferase assay further demonstrated that PDTC treatment markedly inhibited the activity of the CXCL16 promoter. In conclusion, CXCL16, whose transcription was enhanced by LPS, may be involved in ROS production, epithelial barrier dysfunction and E-cadherin down-regulation via p38 signalling, thus contributing to the pathogenesis of ALI. Importantly, CXCR6 knockout or inhibition of p38 signalling may protect mice from LPS-induced lung injury by decreasing E-cadherin expression.

关键词16HBE ; CXCL16 ; NF-κB ; acute lung injury ; p38 signal

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6653424/

 

 

编号:17

题名:Anomalin attenuates LPS-induced acute lungs injury through inhibition of AP-1 signaling.

异常素通过抑制AP-1信号传导减弱LPS诱导的急性肺损伤

作者:Khan, A;Khan, S;Ali, H;Shah, KU;Ali, H;Shehzad, O;Onder, A;Kim, YS

出处:Int Immunopharmacol.2019,73:451-460

IF3.361

摘要:  In the present study, the anomalin was investigated to determine the protective effects and underlying mechanism against LPS-induced acute lung injury in mice. Anomalin administration 30?min after the LPS injection, significantly attenuated the mechanical allodynia, decrease body temperature, and improved the histological changes and inhibited the infiltration of leukocytes. The anomalin treatment markedly inhibited the production of pro-inflammatory mediators such as cytokines (IL-1β, IL-6 and TNF-α) and NO in contrast to the LPS treated groups. Similarly, the anomalin also enhanced the level of anti-oxidant enzymes such as GST, GSH, Catalase and inhibited oxidative stress marker such as MDA. In order to explore the molecular mechanism the effect of anomalin was evaluated for mitogen activated protein kinases (MAPK) in LPS-stimulated RAW264.7 cells. The anomalin treatment significantly attenuated the MAPK proteins such as ERK1/2, JNK and p38 (which is downstream signaling proteins to the MAPKKKs and MAPKKs protein) in the RAW264.7 macrophages using western blot analysis. Furthermore, the western blot analysis showed that anomalin treatment significantly inhibited the activation of the Akt proteins in the RAW264.7 macrophages. The AP-1 served as downstream target for the MAPK pathways and the blocking MAPK pathways is responsible for the inhibition of the AP-1 protein. The AP-1/DNA binding was assessed in the RAW264.7 cells using EMSA. The anomalin treatment significantly restricted the AP-1/DNA binding activity and the decrease in the AP-1/DNA binding activity might be contributed due to the upstream inhibition of the MAPKs signaling.

主题词:Acute Lung Injury/metabolism*/急性肺损伤/代谢*

主题词:Coumarins/pharmacology*/香豆素类/药理学*

主题词:Lipopolysaccharides/脂多糖类

主题词:Mitogen-Activated Protein Kinases/metabolism/丝裂原激活蛋白激酶类/代谢

主题词:Transcription Factor AP-1/antagonists & inhibitors*/转录因子AP-1/拮抗剂与抑制剂*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:18

题名:Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-κB Signaling Pathway Mediated by p38 MAPK and Akt.

去氢木香内酯通过p38 MAPKAkt介导的NF-κB信号通路抑制LPS诱导的急性肺损伤和巨噬细胞活化

作者:Nie, Y;Wang, Z;Chai, G;Xiong, Y;Li, B;Zhang, H;Xin, R;Qian, X;Tang, Z;Wu, J;Zhao, P

出处:Molecules.2019,24(8):

IF3.06

摘要:  Acute lung injury (ALI) is a severe clinical disease marked by dysregulated inflammation response and has a high rate of morbidity and mortality. Macrophages, which play diverse roles in the inflammatory response, are becoming therapeutic targets in ALI. In this study we investigated the effects of dehydrocostus lactone (DHL), a natural sesquiterpene, on macrophage activation and LPS-induced ALI. The macrophage cell line RAW264.7 and primary lung macrophages were incubated with DHL (0, 3, 5, 10 and 30 μmol/L) for 0.5 h and then challenged with LPS (100 ng/mL) for up to 8 hours. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI) and then treated with a range of DHL doses intraperitoneally (5 to 20 mg/kg). The results showed that DHL inhibited LPS-induced production of proinflammatory mediators such as iNOS, NO, and cytokines including TNF-α, IL-6, IL-1β, and IL-12 p35 by suppressing the activity of NF-κB via p38 MAPK/MK2 and Akt signaling pathway in macrophages. The in vivo results revealed that DHL significantly attenuated LPS-induced pathological injury and reduced cytokines expression in the lung. NF-κB, p38 MAPK/MK2 and Akt signaling molecules were also involved in the anti-inflammatory effect. Collectively, our findings suggested that DHL is a promising agent for alleviating LPS-induced ALI.

主题词:Acute Lung Injury*/chemically induced/急性肺损伤*/化学诱导

主题词:Acute Lung Injury*/metabolism/急性肺损伤*/代谢

主题词:Acute Lung Injury*/pathology/急性肺损伤*/病理学

主题词:Acute Lung Injury*/prevention & control/急性肺损伤*/预防与控制

主题词:Anti-Inflammatory Agents/pharmacology*/消炎药/药理学*

主题词:Lactones/pharmacology*/内酯类/药理学*

主题词:Lipopolysaccharides/toxicity*/脂多糖类/毒性*

主题词:MAP Kinase Signaling System/drug effects*/MAP激酶信号系统/药物作用*

主题词:Macrophage Activation/drug effects*/巨噬细胞活化/药物作用*

主题词:Macrophages/metabolism*/巨噬细胞/代谢*

主题词:Sesquiterpenes/pharmacology*/倍半萜类/药理学*

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514677/

 

 

编号:19

题名:Penehyclidine hydrochloride alleviates lipopolysaccharide-induced acute lung injury in rats: Potential role of caveolin-1 expression upregulation.

盐酸戊乙奎醚减轻脂多糖诱导的大鼠急性肺损伤:caveolin-1表达上调的潜在作用

作者:Wu, X;Kong, Q;Xia, Z;Zhan, L;Duan, W;Song, X

出处:Int J Mol Med.2019,43(5):2064-2074

IF2.928

摘要:  The aim of the present study was to examine the protective effect of caveolin-1 (Cav-1) in the penehyclidine hydrochloride (PHC)-based inhibition of lipopolysaccharide (LPS)?induced acute lung injury (ALI) in vivo and in vitro, in addition to the potential underlying mechanisms. In vivo, an ALI rat model was established via intratracheal administration of LPS (5 mg/kg), and PHC (2 mg/kg) was administered 30 min following LPS treatment. In vitro, the Cav-1 gene was knocked down by small interfering (si)RNA in J774A.1 cells. Cells were incubated with LPS (1µg/ml) for 2 h, and subsequently incubated with PHC (2µg/ml) for an additional 2 h. Lung injury was assessed by lung histology and the ratio of polymorphonuclear leukocytes (PMNs) to total cells was assessed in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activity, BALF protein content and lung wet/dry (W/D) ratio. The levels of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β, in the sera of rats and cell culture supernatant were determined by ELISA. The protein expression levels of Cav-1, toll?like receptor 4 (TLR4), phosphorylated (p)-p38 mitogen activated protein kinases (p38 MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells transcription factor p65 subunit (NF-κB p65) in lung tissues and J774A.1 cells were analyzed by western blot analysis. The results indicated that PHC effectively alleviated lung injury by decreasing neutrophil infiltration and protein concentration in BALF, and the lung W/D ratio and MPO activity and pro?inflammatory cytokine production induced by LPS. Furthermore, PHC significantly decreased the degrees of histopathological changes and pulmonary dysfunction. In?vitro, treatment with PHC inhibited pro-inflammatory cytokine levels and MPO activity in LPS?stimulated J774A.1 cells. However, the results in the J774A.1 cells with Cav-1 gene knockdown were contrary. In addition, PHC decreased TLR4, p-p38 MAPKs and nuclear NF-κB p65 expression levels and upregulated the expression level of Cav-1, in?vivo and in vitro. These data demonstrated that PHC exhibited a protective effect against LPS?induced ALI in rats and LPS-stimulated J774A.1 cells, which may be due to the inhibition of p38 MAPKs phosphorylation and TLR4/NF-κB signaling pathway by Cav-1 upregulation.

主题词:Acute Lung Injury/drug therapy*/急性肺损伤/药物疗法*

主题词:Acute Lung Injury/metabolism*/急性肺损伤/代谢*

主题词:Caveolin 1/metabolism*/窖蛋白1/代谢*

主题词:Lipopolysaccharides/脂多糖类

主题词:Quinuclidines/therapeutic use*/奎宁环类/治疗应用*

主题词:Up-Regulation*/drug effects/增量调节*/药物作用

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443352/

 

 

编号:20

题名:Nimbolide protects against endotoxin-induced acute respiratory distress syndrome by inhibiting TNF-α mediated NF-κB and HDAC-3 nuclear translocation.

印苦楝内酯通过抑制TNF-α介导的NF-κBHDAC-3核转位来预防内毒素诱导的急性呼吸窘迫综合征

作者:Pooladanda, V;Thatikonda, S;Bale, S;Pattnaik, B;Sigalapalli, DK;Bathini, NB;Singh, SB;Godugu, C

出处:Cell Death Dis.2019,10(2):81

IF5.959

摘要:  Acute respiratory distress syndrome (ARDS) is characterized by an excessive acute inflammatory response in lung parenchyma, which ultimately leads to refractory hypoxemia. One of the earliest abnormalities seen in lung injury is the elevated levels of inflammatory cytokines, among them, the soluble tumor necrosis factor (TNF-α) has a key role, which exerts cytotoxicity in epithelial and endothelial cells thus exacerbates edema. The bacterial lipopolysaccharide (LPS) was used both in vitro (RAW 264.7, THP-1, MLE-12, A549, and BEAS-2B) and in vivo (C57BL/6 mice), as it activates a plethora of overlapping inflammatory signaling pathways involved in ARDS. Nimbolide is a chemical constituent of Azadirachta indica, which contains multiple biological properties, while its role in ARDS is elusive. Herein, we have investigated the protective effects of nimbolide in abrogating the complications associated with ARDS. We showed that nimbolide markedly suppressed the nitrosative-oxidative stress, inflammatory cytokines, and chemokines expression by suppressing iNOS, myeloperoxidase, and nitrotyrosine expression. Moreover, nimbolide mitigated the migration of neutrophils and mast cells whilst normalizing the LPS-induced hypothermia. Also, nimbolide modulated the expression of epigenetic regulators with multiple HDAC inhibitory activity by suppressing the nuclear translocation of NF-κB and HDAC-3. We extended our studies using?molecular docking studies, which demonstrated a strong interaction between nimbolide and TNF-α. Additionally, we showed that treatment with nimbolide increased GSH, Nrf-2, SOD-1, and HO-1 protein expression; concomitantly abrogated the LPS-triggered TNF-α, p38 MAPK, mTOR, and GSK-3β protein expression. Collectively, these results indicate that TNF-α-regulated NF-κB and HDAC-3 crosstalk was ameliorated by nimbolide with promising anti-nitrosative, antioxidant, and anti-inflammatory properties in LPS-induced ARDS.

主题词:Azadirachta/chemistry*/印楝属/化学*

主题词:Limonins/therapeutic use*/柠檬苦素类/治疗应用*

主题词:Molecular Docking Simulation/methods*/分子对接模拟/方法*

主题词:Respiratory Distress Syndrome, Adult/drug therapy*/呼吸窘迫综合征, 成人/药物疗法*

主题词:Respiratory Distress Syndrome, Adult/genetics*/呼吸窘迫综合征, 成人/遗传学*

主题词:Tumor Necrosis Factor-alpha/antagonists & inhibitors*/肿瘤坏死因子α/拮抗剂与抑制剂*

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349848/

 

 

编号:21

题名:Obeticholic acid alleviate lipopolysaccharide-induced acute lung injury via its anti-inflammatory effects in mice.

奥贝胆酸通过其抗炎作用减轻小鼠脂多糖诱导的急性肺损伤

作者:Fei, J;Fu, L;Hu, B;Chen, YH;Zhao, H;Xu, DX;Li, JB

出处:Int Immunopharmacol.2019,66:177-184

IF3.361

摘要:  Acute lung injury (ALI) is a common disease that may result in acute respiratory failure and death. However, there are still no effective treatments for ALI. Several studies have shown that farnesoid X receptor (FXR) has an anti-inflammatory effect. We investigated the effects of obeticholic acid (OCA), an agonist of FXR, on Lipopolysaccharide (LPS)-induced ALI in mice. Sixty male mice were randomly divided into six groups, and orally administered with or without OCA once daily for 3 consecutive days before LPS (1.0mg/kg). Animals were sacrificed at 0h, 2h or 6h after LPS. As expected, OCA enhanced pulmonary FXR activity. OCA prevented LPS-induced ALI. Additional experiment showed that OCA alleviated LPS-induced up-regulation of pulmonary pro-inflammatory and chemokine genes. Moreover, OCA also repressed LPS-induced the release of TNF-α and KC in serum and bronchoalveolar lavage fluid. In contrast, OCA further up-regulated LPS-induced the expression of Il-10, an anti-inflammatory cytokine. Further study showed that OCA inhibited LPS-evoked NF-κB signaling in the lungs. OCA attenuated LPS-induced ERK1/2, JNK, p38 and Akt phosphorylation in the lungs. Overall, these results suggest that OCA prevent LPS-induced ALI may be through enhancing pulmonary FXR activity and then blockading several inflammatory signaling pathways.

主题词:Acute Lung Injury/drug therapy*/急性肺损伤/药物疗法*

主题词:Anti-Inflammatory Agents/therapeutic use*/消炎药/治疗应用*

主题词:Chenodeoxycholic Acid/analogs & derivatives*/鹅脱氧胆酸/类似物与衍生物*

主题词:Inflammation/drug therapy*/炎症/药物疗法*

主题词:Lipopolysaccharides/immunology/脂多糖类/免疫学

主题词:Lung/drug effects*//药物作用*

主题词:NF-kappa B/metabolism/NF-κB/代谢

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编号:22

题名:Epicatechin alleviates inflammation in lipopolysaccharide-induced acute lung injury in mice by inhibiting the p38 MAPK signaling pathway.

表儿茶素通过抑制p38MAPK信号传导途径减轻脂多糖诱导的小鼠急性肺损伤中的炎症

作者:Xing, J;Yu, Z;Zhang, X;Li, W;Gao, D;Wang, J;Ma, X;Nie, X;Wang, W

出处:Int Immunopharmacol.2019,66:146-153

IF3.361

摘要:  The p38 MAPK signaling pathway plays a key role in lung inflammation and the development of acute lung injury (ALI). We previously reported that the phenolic compound procyanidin B1 inhibits inflammation by suppressing the p38 MAPK signaling pathway. Here, we asked whether the monomer of procyanidin B1, epicatechin (EC), can alleviate LPS-induced ALI in mice, and if so, whether EC acts by inhibiting p38 MAPK. C57BL/6 mice were randomly divided into four groups (n=8) and received EC alone, vehicle (sham group), LPS alone, or LPS and EC. LPS was administered via intraperitoneal injection and EC via nasogastric feeding. Lung histopathology, alveolocapillary membrane permeability, inflammation, and p38 MAPK pathway activation were assessed by immunohistochemistry, tissue wet/dry weight analysis, quantitative PCR, protein assays, ELISA, and western blot analysis using lung tissue and/or bronchoalveolar fluid. We also performed molecular modeling and in vitro enzymatic assays to examine the potential interaction between EC and p38 MAPK at the molecular level. We found that LPS caused an increase in ALI-associated lung pathology accompanied by activation of p-p38 pathway components and the transcription factor AP1. All of these effects were substantially reduced by treatment with EC. Furthermore, molecular modeling suggested that EC suppressed p38 MAPK signaling by hydrogen bonding with Glu71, Ala 111, Asp112, and Leu171 in the active site of p38α. In vitro kinase assays confirmed the ability of EC to directly inhibit purified p38 MAPK. Collectively, our data suggest that the naturally occurring compound EC could be a new therapeutic option for ALI.

主题词:Acute Lung Injury/drug therapy*/急性肺损伤/药物疗法*

主题词:Anti-Inflammatory Agents/therapeutic use*/消炎药/治疗应用*

主题词:Catechin/therapeutic use*/儿茶素/治疗应用*

主题词:Inflammation/drug therapy*/炎症/药物疗法*

主题词:Lipopolysaccharides/immunology/脂多糖类/免疫学

主题词:p38 Mitogen-Activated Protein Kinases/metabolism*/p38丝裂原活化蛋白激酶类/代谢*

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编号:23

题名:Tannic acid protects against experimental acute lung injury through downregulation of TLR4 and MAPK.

单宁酸通过下调TLR4MAPK来预防实验性急性肺损伤

作者:Sivanantham, A;Pattarayan, D;Bethunaickan, R;Kar, A;Mahapatra, SK;Thimmulappa, RK;Palanichamy, R;Rajasekaran, S

出处:J Cell Physiol.2019,234(5):6463-6476

IF4.522

摘要:  Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) remain a major cause of morbidity and mortality in critically ill patients, and no specific therapies are still available to control the mortality rate. Thus, we explored the preventive and therapeutic effects of tannic acid (TA), a natural polyphenol in the context of ALI. We used in vivo and in vitro models, respectively, using lipopolysaccharide (LPS) to induce ALI in mice and exposing J774 and BEAS-2B cells to LPS. In both preventive and therapeutic approaches, TA attenuated LPS-induced histopathological alterations, lipid peroxidation, lung permeability, infiltration of inflammatory cells, and the expression of proinflammatory mediators. In addition, in-vitro study showed that TA treatment could reduce the expression of proinflammatory mediators. Further studies revealed that TA-dampened inflammatory responses by downregulating the LPS-induced toll-like receptor 4 (TLR4) expression and inhibiting?extracellular-signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) activation. Furthermore, cells treated with the inhibitors of ERK1/2 (PD98059) and p38 (SB203580) mitigated the expression of cytokines induced by LPS, thus suggesting that ERK1/2 and p38 activity are required for the inflammatory response. In conclusion, TA could attenuate LPS-induced inflammation and may be a potential therapeutic agent for ALI-associated inflammation in clinical settings.

主题词:Acute Lung Injury/pathology*/急性肺损伤/病理学*

主题词:Mitogen-Activated Protein Kinases/biosynthesis*/丝裂原激活蛋白激酶类/生物合成*

主题词:Tannins/pharmacology*/单宁类/药理学*

主题词:Toll-Like Receptor 4/biosynthesis*/Toll样受体4/生物合成*

主题词:Toll-Like Receptor 4/drug effects/Toll样受体4/药物作用

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编号:24

题名:Magnoflorine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Suppressing NF-κB and MAPK Activation.

木兰花碱通过抑制NF-κBMAPK活化来改善脂多糖诱导的急性肺损伤

作者:Guo, S;Jiang, K;Wu, H;Yang, C;Yang, Y;Yang, J;Zhao, G;Deng, G

出处:Front Pharmacol.2018,9:982

IF3.845

摘要:  Acute lung injury (ALI) which is featured by a strong pulmonary inflammation, is a major cause of morbidity and mortality in critically ill patients. Magnoflorine, a quaternary alkaloid isolated from Chinese herb Magnolia or Aristolochia, has been reported to have potent anti-inflammatory properties. However, the effect of magnoflorine on lipopolysaccharide (LPS)-induced ALI in mice has not been reported. The purpose of the present study is to investigate the anti-inflammatory effect of magnoflorine on LPS-induced ALI and elucidate its possible molecular mechanisms in RAW264.7 cells. The results of histopathological changes as well as the myeloperoxidase (MPO) activity indicated that magnoflorine significantly alleviated the lung injury induced by LPS. In addition, qPCR results showed that magnoflorine dose-dependently decreased the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Immunofluorescence assay also confirmed that the level of Toll-like receptor 4 (TLR4) induced by LPS was inhibited by magnoflorine treatment. Further experiments were performed using Western blotting to detect the expression of related proteins in the NF-κB and MAPK signaling pathways. The results showed that magnoflorine suppressed the levels of phosphorylated p65, IκBα, p38, ERK, and JNK. In conclusion, all data indicate that magnoflorine could protect against LPS-induced inflammation in ALI at least partially by inhibiting TLR4-mediated NF-κB and MAPK signaling pathways.

关键词ALI ; LPS ; MAPK ; NF-κB ; anti-inflammation ; magnoflorine

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125611/

 

 

编号:25

题名:Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury.

在急性肺损伤小鼠模型中通过p38MAPK信号传导途径调节NLRP3炎性体和巨噬细胞焦痂

作者:Li, D;Ren, W;Jiang, Z;Zhu, L

出处:Mol Med Rep.2018,18(5):4399-4409

IF1.851

摘要:  Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is characterized by uncontrolled progressive lung inflammation. Macrophages serve a key role in the pathogenesis of ALI/ARDS. Macrophage pyroptosis is a process of cell death releasing the proinflammatory cytokines interleukin (IL)-1β and IL-18. It was hypothesized that macrophage pyroptosis may partially account for the uncontrolled lung inflammation of ALI/ARDS. In the present study, greater macrophage pyroptosis in lipopolysaccharide (LPS)-treated macrophages and the ALI/ARDS mouse model was observed. The expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing (NLRP)3 and IL-1β and cleavage of caspase-1 were significantly elevated following LPS treatment accompanied by greater activation of p38 mitogen-activated protein kinase (MAPK) signaling in vitro and in vivo. However, blocking p38 MAPK signaling through the inhibitor SB203580 significantly suppressed the acute lung injury and excessive lung inflammation in vivo, consistent with the reduced expression of the NLRP3 inflammasome and IL-1β and cleavage of caspase-1. Pretreatment of the rat NR8383 macrophage cell line with SB203580 significantly decreased the population of caspase-1+PI+ pyroptotic cells and expression of NLRP3/IL-1β. However, a larger population of Annexin V+PI- apoptotic cells was observed following blocking of the p38 MAPK signaling pathway. The results indicated that blockage of p38 MAPK signaling pathway skewed macrophage cell death from proinflammatory pyroptosis towards non?inflammatory apoptosis. These effects may contribute to attenuated acute lung injury and excessive inflammation in the SB203580?treated mice. The results may provide a novel therapeutic strategy for the treatment of uncontrolled lung inflammation in patients with ALI/ARDS.

主题词:Acute Lung Injury/drug therapy*/急性肺损伤/药物疗法*

主题词:Interleukin-1beta/genetics*/白细胞介素1β/遗传学*

主题词:NLR Family, Pyrin Domain-Containing 3 Protein/genetics*/NLR家族,PYRIN域含蛋白质3/遗传学*

主题词:Respiratory Distress Syndrome, Adult/drug therapy*/呼吸窘迫综合征, 成人/药物疗法*

主题词:p38 Mitogen-Activated Protein Kinases/genetics*/p38丝裂原活化蛋白激酶类/遗传学*

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172370/

 

 

编号:26

题名:AIBP augments cholesterol efflux from alveolar macrophages to surfactant and reduces acute lung inflammation.

AIBP增加胆固醇从肺泡巨噬细胞外流到表面活性物质并减少急性肺部炎症

作者:Choi, SH;Wallace, AM;Schneider, DA;Burg, E;Kim, J;Alekseeva, E;Ubags, ND;Cool, CD;Fang, L;Suratt, BT;Miller, YI

出处:JCI Insight.2018,3(16):

IF6.014

摘要:  Acute respiratory distress syndrome (ARDS) is characterized by an excessive pulmonary inflammatory response. Removal of excess cholesterol from the plasma membrane of inflammatory cells helps reduce their activation. The secreted apolipoprotein A-I binding protein (AIBP) has been shown to augment cholesterol efflux from endothelial cells to the plasma lipoprotein HDL. Here, we find that AIBP was expressed in inflammatory cells in the human lung and was secreted into the bronchoalveolar space in mice subjected to inhalation of LPS. AIBP bound surfactant protein B and increased cholesterol efflux from alveolar macrophages to calfactant, a therapeutic surfactant formulation. In vitro, AIBP in the presence of surfactant reduced LPS-induced p65, ERK1/2 and p38 phosphorylation, and IL-6 secretion by alveolar macrophages. In vivo, inhalation of AIBP significantly reduced LPS-induced airspace neutrophilia, alveolar capillary leak, and secretion of IL-6. These results suggest that, similar to HDL in plasma, surfactant serves as a cholesterol acceptor in the lung. Furthermore, lung injury increases pulmonary AIBP expression, which likely serves to promote cholesterol efflux to surfactant and reduce inflammation.

主题词:Apolipoprotein A-I/metabolism*/载脂蛋白A-Ⅰ/代谢*

主题词:Macrophages, Alveolar/immunology*/巨噬细胞, 肺泡/免疫学*

主题词:Pneumonia, Bacterial/immunology*/肺炎, 细菌性/免疫学*

主题词:Racemases and Epimerases/metabolism*/消旋酶类和差向异构酶类/代谢*

主题词:Respiratory Distress Syndrome, Adult/immunology*/呼吸窘迫综合征, 成人/免疫学*

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141166/

 

 

编号:27

题名:Zerumbone from Zingiber zerumbet Ameliorates Lipopolysaccharide-Induced ICAM-1 and Cytokines Expression via p38 MAPK/JNK-IκB/NF-κB Pathway in Mouse Model of Acute Lung Injury.

姜姜中的花姜酮通过p38 MAPK /JNK-IκB/NF-κB途径改善了急性肺损伤小鼠模型中脂多糖诱导的ICAM-1和细胞因子的表达

作者:Lee, CY;Chen, SP;Su, CH;Ho, YC;Yang, ML;Lee, SS;Huang-Liu, R;Yang, CP;Chen, CJ;Kuan, YH

出处:Chin J Physiol.2018,61(3):171-180

IF1.108

摘要:  Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality rates mainly caused by Gram-negative bacteria. Nevertheless, an effective treatment strategy for ALI is yet to be developed. Zerumbone, a sesquiterpene isolated from Zingiber zerumbet Smith, possesses several advantageous bioeffects such as antioxidation, anti-inflammation, and antiulcer. Pretreatment of zerumbone inhibited lipopolysaccharide (LPS)-induced arterial blood gas exchange, neutrophils infiltration, and increased pulmonary vascular permeability. LPS-induced expression of intercellular adhesion molecule-1 (ICAM-1) was inhibited by zerumbone at a lower concentration than that of vascular cell adhesion molecule-1 (VCAM-1). In addition, proinflammatory cytokines, such as interleukin (IL)-1β and macrophage inflammatory protein (MIP)-2 were suppressed by zerumbone. The phosphorylation of nuclear factor (NF)-κB, a proinflammatory transcription factor, and degradation of inhibitor of κB (IκB), an inhibitor of NF-κB, were also reduced by zerumbone. Furthermore, we found the inhibitory concentration of zerumbone on phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was lower than that of extracellular signal-regulated kinase (ERK). In conclusion, zerumbone could be a potential protective agent for ALI, possibly via expression of ICAM-1, IL-1β, and MIP-2. The protective mechanism of zerumbone was by reversing the activation of p38 MAPK/JNK-IκB/NF-κB pathway.

主题词:Acute Lung Injury/prevention & control*/急性肺损伤/预防与控制*

主题词:Anti-Inflammatory Agents/pharmacology*/消炎药/药理学*

主题词:Cytokines/metabolism*/细胞因子类/代谢*

主题词:I-kappa B Proteins/metabolism*/I-κB蛋白质类/代谢*

主题词:Intercellular Adhesion Molecule-1/metabolism*/胞间黏附分子1/代谢*

主题词:JNK Mitogen-Activated Protein Kinases/metabolism*/JNK丝裂原活化蛋白激酶类/代谢*

主题词:Lipopolysaccharides*/脂多糖类*

主题词:Lung/drug effects*//药物作用*

主题词:NF-kappa B/metabolism*/NF-κB/代谢*

主题词:Plant Extracts/pharmacology*/植物提取物/药理学*

主题词:Sesquiterpenes/pharmacology*/倍半萜类/药理学*

主题词:Zingiberaceae*/chemistry/姜科*/化学

主题词:p38 Mitogen-Activated Protein Kinases/metabolism*/p38丝裂原活化蛋白激酶类/代谢*

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编号:28

题名:Costunolide ameliorates lipoteichoic acid-induced acute lung injury via attenuating MAPK signaling pathway.

木香烃内酯通过减弱MAPK信号通路改善脂磷壁酸诱导的急性肺损伤

作者:Chen, Z;Zhang, D;Li, M;Wang, B

出处:Int Immunopharmacol.2018,61:283-289

IF3.361

摘要:  Lipoteichoic acid (LTA)-induced acute lung injury (ALI) is an experimental model for mimicking Gram-positive bacteria-induced pneumonia that is a refractory disease with lack of effective medicines. Here, we reported that costunolide, a sesquiterpene lactone, ameliorated LTA-induced ALI. Costunolide treatment reduced LTA-induced neutrophil lung infiltration, cytokine and chemokine production (TNF-α, IL-6 and KC), and pulmonary edema. In response to LTA challenge, treatment with costunolide resulted less iNOS expression and produced less inflammatory cytokines in bone marrow derived macrophages (BMDMs). Pretreatment with costunolide also attenuated the LTA-induced the phosphorylation of p38 MAPK and ERK in BMDMs. Furthermore, costunolide treatment reduced the phosphorylation of TAK1 and inhibited the interaction of TAK1 with Tab1. In conclusion, we have demonstrated that costunolide protects against LTA-induced ALI via inhibiting TAK1-mediated MAPK signaling pathway, and our studies suggest that costunolide is a promising agent for treatment of Gram-positive bacteria-mediated pneumonia.

主题词:Anti-Inflammatory Agents/therapeutic use*/消炎药/治疗应用*

主题词:Chemical and Drug Induced Liver Injury/drug therapy*/药物引起的肝损伤/药物疗法*

主题词:Gram-Positive Bacteria/physiology*/革兰氏阳性菌/生理学*

主题词:Lipopolysaccharides/脂多糖类

主题词:Lung/drug effects*//药物作用*

主题词:Macrophages/drug effects*/巨噬细胞/药物作用*

主题词:Pneumonia, Bacterial/drug therapy*/肺炎, 细菌性/药物疗法*

主题词:Pulmonary Edema/drug therapy*/肺水肿/药物疗法*

主题词:Sesquiterpenes/therapeutic use*/倍半萜类/治疗应用*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:29

题名:The protective effect of lidocaine on lipopolysaccharide-induced acute lung injury in rats through NF-κB and p38 MAPK signaling pathway and excessive inflammatory responses.

利多卡因通过NF-κBp38 MAPK信号通路及过度炎症反应对脂多糖诱导的大鼠急性肺损伤的保护作用

作者:Chen, LJ;Ding, YB;Ma, PL;Jiang, SH;Li, KZ;Li, AZ;Li, MC;Shi, CX;Du, J;Zhou, HD

出处:Eur Rev Med Pharmacol Sci.2018,22(7):2099-2108

IF2.721

摘要:  OBJECTIVE:Acute lung injury is a severe disease with a high rate of mortality, leading to more important illness. We aimed at exploring the protective role and potential mechanisms of lidocaine on lipopolysaccharide (LPS)-induced acute lung injury (ALI). MATERIALS AND METHODS:Sprague Dawley (SD) rats were randomly assigned to control group receiving 0.9% saline solution, LPS group treated with 4 mg/kg LPS i.p., LPS + lidocaine(treated with 4 mg/kg LPS i.p. followed by giving 1 mg/kg, 3 mg/kg, 5 mg/kg of lidocaine i.v.). Lung specimens and the bronchoalveolar lavage fluid (BALF) were collected for histopathological examination and biochemical analyze 12 h after LPS induction. The cytokines expression of TNF-α, IL-6 and MCP-1 was measured by ELISA. In addition, the malondialdehyde (MDA) content, the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in lung tissues were also detected using ELISA. The protein expressions of p38, p-p38, p65, p-p65 and IκB were analyzed by Western blot. RESULTS:The results indicated that after lidocaine treatment was able to decrease significantly wet-to-dry (W/D) ratio and ameliorate the histopathologic damage. Additionally, total protein content and the number of leukocytes in BALF significantly decreased. ELISA result indicated that the levels of TNF-α, IL-6 and MCP-1 in BALF were markedly suppressed. Meanwhile, the activities of T-AOC and SOD in lung tissues significantly increased, while the content of MDA significantly decreased after treatment with lidocaine. Moreover, Western blot suggested that lidocaine inhibited phosphorylation of NF-κB p65 and p38 MAPK. CONCLUSIONS:Therefore, lidocaine could ameliorate the LPS-induced lung injury via NF-κB/p38 MAPK signaling and excessive inflammatory responses, providing a potential for becoming the anti-inflammatory agent against lung injury.

主题词:Acute Lung Injury/prevention & control*/急性肺损伤/预防与控制*

主题词:Inflammation Mediators/antagonists & inhibitors*/炎症介导素类/拮抗剂与抑制剂*

主题词:Lidocaine/therapeutic use*/利多卡因/治疗应用*

主题词:Lipopolysaccharides/toxicity/脂多糖类/毒性

主题词:NF-kappa B/antagonists & inhibitors*/NF-κB/拮抗剂与抑制剂*

主题词:Signal Transduction/drug effects*/信号传导/药物作用*

主题词:p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors*/p38丝裂原活化蛋白激酶类/拮抗剂与抑制剂*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:30

题名:Protective effect of dihydromyricetin on LPS-induced acute lung injury.

二氢杨梅素对脂多糖引起的急性肺损伤的保护作用

作者:Wang, B;Xiao, Y;Yang, X;He, Y;Jing, T;Wang, W;Zhang, J;Lin, R

出处:J Leukoc Biol.2018:

IF4.012

摘要:  Dihydromyricetin (DHM), a bioactive flavonoid component isolated from Ampelopsis grossedentata, is known to have anti-inflammatory effect, but the effect of DHM on acute lung injury (ALI) is largely unknown. Here, we investigated the effect of DHM on ALI and the underlying mechanism by bioinformatic analyses and animal experiments. We found that pretreatment with DHM ameliorated lung pathological changes and suppressed the inflammation response in lung tissues after LPS challenge. The potential targets of DHM were predicted by DDI-CPI and DRAR-CPI tools and analyzed using the STRING server to predict the functionally related signaling pathways, such as MAPK signaling. Molecular docking calculations indicated that DHM could be embedded tightly into the binding pocket of ERK, JNK, and p38. Furthermore, the activation of MAPK signaling induced by LPS was inhibited by DHM. In conclusion, these findings suggest that DHM may exert its protective effect on ALI by inhibiting MAPK signaling. The present study supports a potential clinical application for DHM in treating ALI and provides a novel design that combines in silico methods with in vivo experiments for drug research.

关键词MAPK ; acute lung injury ; bioinformatics ; dihydromyricetin ; inflammation ; protective effect

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编号:31

题名:New thiazolidinedione LPSF/GQ-2 inhibits NFκB and MAPK activation in LPS-induced acute lung inflammation.

新噻唑烷二酮LPSF / GQ-2抑制LPS诱导的急性肺部炎症中的NFκBMAPK活化

作者:Santos, LAMD;Rodrigues, GB;Mota, FVB;Fran?a, MER;de Souza Barbosa, KP;Oliveira, WH;Rocha, SWS;Lós, DB;Silva, AKS;Silva, TGD;Peixoto, CA

出处:Int Immunopharmacol.2018,57:91-101

IF3.361

摘要:  Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are responsible for high mortality rates in critical patients. Despite >50?years of intensive research, there is no pharmacologically effective treatment to treat ALI. PPARs agonists, chemically named thiazolidinediones (TZDs) have emerged as potential drugs for the treatment of ALI and ARDS due to their anti-inflammatory efficacy. The present study aims to evaluate the potential anti-inflammatory effects of new TZDs derivatives, LPSF/GQ-2 and LPSF/RA-4, on ALI induced by LPS. BALB/c mice were divided into five groups: 1) Control; 2) LPS intranasal 25μg; 3) LPSF/GQ-2 30mg/kg+LPS; 4) LPSF/RA-4 20?mg/kg+LPS; and 5) DEXA 1mg/Kg+LPS. BALF analyses revealed that LPSF/GQ-2 and LPSF/RA-4 reduced NO levels in BALF and inflammatory cell infiltration induced by LPS. MPO levels were also reduced by the LPSF/GQ-2 and LPSF/RA-4 pre-treatments. In contrast, histopathological analyses showed better tissue protection with LPSF/GQ-2 than DEXA and LPSF/RA-4 groups. Similarly, LPSF/GQ-2 reduced inflammatory markers (IL-1, iNOS, TNFα, IL-1β, IL-6) better than LPSF/RA-4. The LPSF/GQ-2 anti-inflammatory action could be attributed to the inhibition of NFκB, ERK, p38, and PARP pathways. In contrast, LPSF/RA-4 had no effect on the expression of p38, JNK, NFκB. The present study indicates that LPSF/GQ-2 presents a potential therapeutic role as an anti-inflammatory drug for ALI.

主题词:Acute Lung Injury/drug therapy*/急性肺损伤/药物疗法*

主题词:Anti-Inflammatory Agents/therapeutic use*/消炎药/治疗应用*

主题词:NF-kappa B/metabolism*/NF-κB/代谢*

主题词:Pneumonia/drug therapy*/肺炎/药物疗法*

主题词:Respiratory Distress Syndrome, Adult/drug therapy*/呼吸窘迫综合征, 成人/药物疗法*

主题词:Thiazolidinediones/therapeutic use*/噻唑烷二酮类/治疗应用*

全文链接:请使用FMRS数据库下载该篇文章。

 

 

编号:32

题名:Protostemonine effectively attenuates lipopolysaccharide-induced acute lung injury in mice.

原百部碱有效减轻脂多糖诱导的小鼠急性肺损伤

作者:Wu, YX;He, HQ;Nie, YJ;Ding, YH;Sun, L;Qian, F

出处:Acta Pharmacol Sin.2018,39(1):85-96

IF4.01

摘要:  Protostemonine (PSN) is the main anti-inflammatory alkaloid extracted from the roots of Stemona sessilifolia (known as "Baibu" in traditional Chinese medicine). Here, we reported the inhibitory effects of PSN on lipopolysaccharide (LPS)-induced macrophage activation in vitro and LPS-induced acute lung injury in mice. Macrophage cell line RAW264.7 cells and mouse bone marrow-derived macrophages (BMDMs) were treated with PSN (1, 3, 10, 30 and 100 μmol/L) for 0.5 h and then challenged with LPS (0.1 μg/mL) for 24 h. Pretreatment with PSN significantly inhibited LPS-induced phosphorylation of MAPKs and AKT, iNOS expression and NO production in the macrophages. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI). The mice were subsequently treated with PSN (10 mg/kg, ip) at 4 and 24 h after LPS challenge. PSN administration significantly attenuated LPS-induced inflammatory cell infiltration, reduced pro-inflammatory cytokine (TNF-α, IL-1β and IL-6) production and eliminated LPS-mediated lung edema. Furthermore, PSN administration significantly inhibited LPS-induced pulmonary MPO activity. Meanwhile, LPS-induced phosphorylation of p38 MAPK, iNOS expression and NO production in the lungs were also suppressed. The results demonstrate that PSN effectively attenuates LPS-induced inflammatory responses in vitro and in vivo; the beneficial effects are associated with the decreased phosphorylation of MAPK and AKT and the reduced expression of pro-inflammatory mediators, such as iNOS, NO and cytokines. These data suggest that PSN may be a potential therapeutic agent in the treatment of ALI.

主题词:Acute Lung Injury/chemically induced/急性肺损伤/化学诱导

主题词:Acute Lung Injury/prevention & control*/急性肺损伤/预防与控制*

主题词:Alkaloids/therapeutic use*/生物碱类/治疗应用*

主题词:Lipopolysaccharides/pharmacology/脂多糖类/药理学

主题词:Macrophages/metabolism/巨噬细胞/代谢

主题词:p38 Mitogen-Activated Protein Kinases/metabolism/p38丝裂原活化蛋白激酶类/代谢

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758663/

 

 

 

 

 

 

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