IL-17A modulates oxidant stress-induced airway hyperresponsiveness but not emphysema.

TitleIL-17A modulates oxidant stress-induced airway hyperresponsiveness but not emphysema.
Publication TypeJournal Article
Year of Publication2013
AuthorsPinart M, Zhang M, Li F, Hussain F, Zhu J, Wiegman C, Ryffel B, Chung K F
JournalPLoS One
Volume8
Issue3
Paginatione58452
Date Published2013
ISSN1932-6203
Abstract

IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R) signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R(-/-) and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours) for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm) and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R(-/-), chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R(-/-) mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R(-/-) mice. p38-mitogen-activated protein kinase (MAPK) and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R(-/-) ozone-exposed mice. Lung inflammation scores were not altered in IL-17R(-/-) mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R(-/-) mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17.

DOI10.1371/journal.pone.0058452
Alternate JournalPLoS ONE
PubMed ID23505509