Airway epithelial integrin β4‐deficiency exacerbates lipopolysaccharide‐induced acute lung injury

2021 ◽  
Author(s):  
Wang Jiang ◽  
Jin‐Mei Wang ◽  
Jin‐Hua Luo ◽  
Yu Chen ◽  
Jiao Pi ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Airway Epithelial ◽  
Integrin Β4

Impaired airway epithelial barrier integrity was mediated by PI3Kδ in a mouse model of lipopolysaccharide-induced acute lung injury

2021 ◽  
Vol 95 ◽  
pp. 107570
Author(s):  
Lihong Yao ◽  
Ying Tang ◽  
Junjie Chen ◽  
Jiahui Li ◽  
Hua Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Integrity

The Attenuation of Murine Acute Lung Injury by Simvastatin Is Mediated by Integrin β4.

2009 ◽  
Author(s):  
W Chen ◽  
S Sammani ◽  
J Zhao ◽  
J Garcia ◽  
J Jacobson
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Integrin Β4

scholarly journals Critical role for integrin-β4 in the attenuation of murine acute lung injury by simvastatin

2012 ◽  
Vol 303 (4) ◽  
pp. L279-L285 ◽  
Author(s):  
Weiguo Chen ◽  
Saad Sammani ◽  
Sumegha Mitra ◽  
Shwu Fan Ma ◽  
Joe G. N. Garcia ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mapk Signaling ◽  
Blue Dye ◽  
Blocking Antibody ◽  
Cell Counts ◽  
Integrin Β4

The statins are a class of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase inhibitors that are recognized to have pleiotropic properties. We previously reported the attenuation of LPS-induced murine acute lung injury (ALI) by simvastatin in vivo and identified relevant effects of simvastatin on endothelial cell (EC) signaling, activation, and barrier function in vitro. In particular, simvastatin induces the upregulation of integrin-β4, which in turn inhibits EC inflammatory responses via attenuation of MAPK signaling. The role of integrin-β4 in murine ALI protection by simvastatin, however, is unknown. We initially confirmed a time- and dose-dependent effect of simvastatin on increased integrin-β4 mRNA expression in human lung EC with peak protein expression evident at 16 h. Subsequently, reciprocal immunoprecipitation demonstrated an attenuation of LPS-induced integrin-β4 tyrosine phosphorylation by simvastatin (5 μM, 16 h). Increased expression of EC inflammatory cytokines [IL-6, IL-8, monocyte chemoattractant protein (MCP)-1, regulated on activation normal T cell expressed and secreted (RANTES)] by LPS (500 ng/ml, 4 h) was also significantly attenuated by simvastatin pretreatment (5 μM, 16 h), but this effect was reversed by cotreatment with an integrin-β4-blocking antibody. Finally, although simvastatin (20 mg/kg) conferred significant protection in murine ALI as evidenced by decreased bronchoalveolar lavage fluid cell counts, protein, inflammatory cytokines (IL-6, IL-1β, MCP-1, RANTES), decreased Evans blue dye albumin extravasation in lung tissue, and changes on lung histology, these effects were reversed by the integrin-β4-blocking antibody (IV, 1 mg/kg, 2 h before LPS). These findings support integrin-β4 as an important mediator of ALI protection by simvastatin and implicate signaling by integrin-β4 as a novel therapeutic target in patients with ALI.

scholarly journals Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Dongdong Liu ◽  
Pu Mao ◽  
Yongbo Huang ◽  
Yiting Liu ◽  
Xiaoqing Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Critical Role ◽  
Model Identification ◽  
Airway Epithelial Cells ◽  
High Morbidity ◽  
Airway Epithelial ◽  
Lps Challenge

Acute respiratory distress syndrome (ARDS) remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI) lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes ofPseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS) challenge in airway epithelial cellsin vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α(TNF-α), whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

scholarly journals Clusterin Deficiency Exacerbates Hyperoxia-Induced Acute Lung Injury

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 944
Author(s):  
Jung Yeon Hong ◽  
Mi Na Kim ◽  
Eun Gyul Kim ◽  
Jae Woo Lee ◽  
Hye Rin Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Mortality Rate ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Intracellular Signaling ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Exposure to high oxygen concentrations leads to generation of excessive reactive oxygen species, causing cellular injury and multiple organ dysfunctions and is associated with a high mortality rate. Clusterin (CLU) is a heterodimeric glycoprotein that mediates several intracellular signaling pathways, including cell death and inflammation. However, the role of CLU in the pathogenesis of hyperoxic acute lung injury (HALI) is unknown. Wild-type (WT) and CLU-deficient mice and cultured human airway epithelial cells were used. Changes in cell death- and inflammation-related molecules with or without hyperoxia exposure in cells and animals were determined. Hyperoxia induced an increase in CLU expression in mouse lungs and human airway epithelial cells. Mice lacking CLU had increased HALI and mortality rate compared with WT mice. In vitro, CLU-disrupted cells showed enhanced release of cytochrome c, Bax translocation, cell death and inflammatory cytokine expression. However, treatment with recombinant CLU attenuated hyperoxia-induced apoptosis. Moreover, the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed metabolic pathways, hematopoietic cell lineage, response to stress and localization and regulation of immune system that were differentially regulated between WT and CLU−/− mice. These results demonstrate that prolonged hyperoxia-induced lung injury is associated with CLU expression and that CLU replenishment may alleviate hyperoxia-induced cell death.

Lipoxin A4 attenuates LPS-induced mouse acute lung injury via Nrf2-mediated E-cadherin expression in airway epithelial cells

2016 ◽  
Vol 93 ◽  
pp. 52-66 ◽  
Author(s):  
Xue Cheng ◽  
Songqing He ◽  
Jing Yuan ◽  
Shuo Miao ◽  
Hongyu Gao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Lipoxin A4 ◽  
E Cadherin

scholarly journals Mitochondria-Modulating Porous Se@SiO2 Nanoparticles Provide Resistance to Oxidative Injury in Airway Epithelial Cells: Implications for Acute Lung Injury

2020 ◽  
Vol Volume 15 ◽  
pp. 2287-2302
Author(s):  
Muyun Wang ◽  
Kun Wang ◽  
Guoying Deng ◽  
Xijian Liu ◽  
Xiaodong Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Oxidative Injury ◽  
Airway Epithelial Cells ◽  
Airway Epithelial
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