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Endoplasmic reticulum stress is a danger signal promoting innate inflammatory responses in bronchial epithelial cells

Endoplasmic reticulum (ER) stress is associated with chronic pulmonary inflammatory diseases. We hypothesized that the combined activation of both Toll-like receptor (TLR) signaling and ER stress might increase inflammatory reactions in otherwise tolerant airway epithelial cells. Indeed, ER stress r...

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Main Authors: Mijošek, Vedrana (Author) , Lasitschka, Felix (Author) , Warth, Arne (Author) , Zabeck, Heike (Author) , Dalpke, Alexander (Author) , Weitnauer, Michael (Author)
Format: Article (Journal)
Language:English
Published: July 16, 2016
In: Journal of innate immunity
Year: 2016, Volume: 8, Issue: 5, Pages: 464-478
ISSN:1662-8128
DOI:10.1159/000447668
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1159/000447668
Verlag, lizenzpflichtig, Volltext: https://www.karger.com/Article/FullText/447668
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Author Notes:Vedrana Mijošek, Felix Lasitschka, Arne Warth, Heike Zabeck, Alexander H. Dalpke, Michael Weitnauer
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Summary:Endoplasmic reticulum (ER) stress is associated with chronic pulmonary inflammatory diseases. We hypothesized that the combined activation of both Toll-like receptor (TLR) signaling and ER stress might increase inflammatory reactions in otherwise tolerant airway epithelial cells. Indeed, ER stress resulted in an increased response of BEAS-2B and human primary bronchial epithelial cells to pathogen-associated molecular pattern stimulation with respect to IL6 and IL8 production. ER stress elevated p38 and ERK MAP kinase activation, and pharmacological inhibition of these kinases could inhibit the boosting effect. Knockdown of unfolded protein response signaling indicated that mainly PERK and ATF6 were responsible for the synergistic activity. Specifically, PERK and ATF6 mediated increased MAPK activation, which is needed for effective cytokine secretion. We conclude that within airway epithelial cells the combined activation of TLR signaling and ER stress-mediated MAPK activation results in synergistic proinflammatory activity. We speculate that ER stress, present in various chronic pulmonary diseases, boosts TLR signaling and therefore proinflammatory cytokine production, thus acting as a costimulatory danger signal.
Item Description:Gesehen am 15.05.2020
Physical Description:Online Resource
ISSN:1662-8128
DOI:10.1159/000447668

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