Cigarette smoke-induced gasdermin D activation in bronchoalveolar macrophages and bronchial epithelial cells dependently on NLRP3.

Details

Serval ID
serval:BIB_03B6B717FE36
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cigarette smoke-induced gasdermin D activation in bronchoalveolar macrophages and bronchial epithelial cells dependently on NLRP3.
Journal
Frontiers in immunology
Author(s)
Huot-Marchand S., Nascimento M., Culerier E., Bourenane M., Savigny F., Panek C., Serdjebi C., Le Bert M., Quesniaux VFJ, Ryffel B., Riteau N., Gombault A., Couillin I.
Contributor(s)
Broz P.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
13
Pages
918507
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Chronic pulmonary inflammation and chronic obstructive pulmonary disease (COPD) are major health issues largely due to air pollution and cigarette smoke (CS) exposure. The role of the innate receptor NLRP3 (nucleotide-binding domain and leucine-rich repeat containing protein 3) orchestrating inflammation through formation of an inflammasome complex in CS-induced inflammation or COPD remains controversial. Using acute and subchronic CS exposure models, we found that Nlrp3-deficient mice or wild-type mice treated with the NLRP3 inhibitor MCC950 presented an important reduction of inflammatory cells recruited into the bronchoalveolar space and of pulmonary inflammation with decreased chemokines and cytokines production, in particular IL-1β demonstrating the key role of NLRP3. Furthermore, mice deficient for Caspase-1/Caspase-11 presented also decreased inflammation parameters, suggesting a role for the NLRP3 inflammasome. Importantly we showed that acute CS-exposure promotes NLRP3-dependent cleavage of gasdermin D in macrophages present in the bronchoalveolar space and in bronchial airway epithelial cells. Finally, Gsdmd-deficiency reduced acute CS-induced lung and bronchoalveolar space inflammation and IL-1β secretion. Thus, we demonstrated in our model that NLRP3 and gasdermin D are key players in CS-induced pulmonary inflammation and IL-1β release potentially through gasdermin D forming-pore and/or pyroptoctic cell death.
Keywords
Animals, Caspase 1/metabolism, Cigarette Smoking/adverse effects, Epithelial Cells/metabolism, Inflammasomes/metabolism, Inflammation/metabolism, Macrophages/metabolism, Mice, NLR Family, Pyrin Domain-Containing 3 Protein/genetics, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Pneumonia/metabolism, Pulmonary Disease, Chronic Obstructive/metabolism, Tobacco/metabolism, NLRP3 inflammasome, cigarette smoke, gasdermin D, lung, mice
Pubmed
Web of science
Open Access
Yes
Create date
12/09/2022 10:56
Last modification date
13/09/2022 6:40
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