Endoplasmic reticulum stress is involved in ventilator-induced lung injury in mice via the IRE1α-TRAF2-NF-κB pathway

Copyright © 2019 Elsevier B.V. All rights reserved..

Inflammation plays a criticalrole in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF),and lung tissue injurywasassessedby histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:78

Enthalten in:

International immunopharmacology - 78(2020) vom: 01. Jan., Seite 106069

Sprache:

Englisch

Beteiligte Personen:

Ye, Liu [VerfasserIn]
Zeng, Qi [VerfasserIn]
Dai, Huijun [VerfasserIn]
Zhang, Weikang [VerfasserIn]
Wang, Xiaoxia [VerfasserIn]
Ma, Riliang [VerfasserIn]
Hong, Xueqi [VerfasserIn]
Zhao, Chen [VerfasserIn]
Pan, Linghui [VerfasserIn]

Links:

Volltext

Themen:

Cytokines
EC 2.7.11.1
EC 3.1.-
Endoplasmic Reticulum Chaperone BiP
Endoplasmic reticulum stress
Endoribonucleases
Ern1 protein, mouse
HSPA5 protein, human
Hspa5 protein, mouse
IRE1α/TRAF2/NF-κB signaling pathway
Inflammation
Journal Article
NF-kappa B
Protein Serine-Threonine Kinases
TNF Receptor-Associated Factor 2
TRAF2 protein, mouse
Ventilator-induced lung injury

Anmerkungen:

Date Completed 13.07.2020

Date Revised 04.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2019.106069

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM30442756X