Endoplasmic reticulum stress mediates environmental particle-induced inflammatory response in bronchial epithelium

Autor: Li Pu, Fen Yi, Wen-jing Yu, Ya-jing Li, You-hui Tu, Ai-hui Xu, Yong Wang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Immunotoxicology, Vol 20, Iss 1 (2023)
Druh dokumentu: article
ISSN: 1547691X
1547-6901
1547-691X
DOI: 10.1080/1547691X.2023.2229428
Popis: AbstractWhile the detailed mechanisms for how particulate matter (PM) causes adverse health effects in the lungs remain largely unknown, endoplasmic reticulum (ER) stress has been implicated in PM-induced lung injury. The present study was undertaken to examine how/if ER stress might regulate PM-induced inflammation, and to begin to define potential underlying molecular mechanisms. Here, ER stress hallmarks were examined in human bronchial epithelial (HBE) cells exposed to PM. To confirm roles of certain pathways, siRNA targeting ER stress genes and an ER stress inhibitor were employed. Expression of select inflammatory cytokines and related signaling pathway components by the cells were assessed as well. The results showed that PM exposure induced elevations in two ER stress hallmarks, i.e. GRP78 and IRE1α, in time-and/or dose-related manners in the HBE cells. Inhibition of ER stress by siRNA for GRP78 or IRE1α significantly alleviated the PM-induced effects. Further, ER stress appeared to regulate PM-induced inflammation – likely through downstream autophagy and NF-κB pathways – as implied by studies showing that inhibition of ER stress by siRNA of GRP78 or IRE1α caused significant amelioration of PM-induced autophagy and subsequent activation of NF-κB pathways. Moreover, the ER stress inhibitor 4-PBA were used to confirm the protective effects against PM-induced outcomes. Together, the results suggest ER stress plays a deleterious role in PM-induced airway inflammation, possibly through activation of autophagy and NF-κB signaling. Accordingly, protocols/treatments that could lead to inhibited ER stress could potentially be effective for treatment of PM-related airway disorders.
Databáze: Directory of Open Access Journals
Externí odkaz: