Contribution of IL-17 to the pulmonary inflammatory response

Abstract

Airway exposure to endotoxin and other microbial Toll-like receptor (TLR) agonists induces a rapid production of mediators including IL-1, neutrophil recruitment and bronchoconstriction, which are abrogated in mice deficient for distinct TLRs or the common adaptor molecule myeloid differentiation factor 88 (MyD88). Intranasal IL-17 administration causes acute neutrophilic lung inflammation in a proinflammatory environment. Recent investigations revealed that IL-17 is up-regulated upon endotoxin aerosol exposure and neutralization of IL-17 diminished endotoxininduced inflammation, suggesting a role of endogenous IL-17 in endotoxin-induced lung inflammation. Furthermore, administration of IL-1β mobilizes neutrophils and induces IL-17 production in the lung. Therefore, IL-17 might participates in IL-1β-induced lung inflammation. Importantly, lung injury leads to NALP3 inflammasome activation, leading to IL-1β-dependent acute inflammation. The participation of IL-17 in this response is discussed. In conclusion, TLR-agonist and injury-induced lung inflammation depend in part on IL-1β and IL-17. The role of inflammasome activation cleaving pro-IL-1β leading to mature IL-1ß and IL-1β-dependent IL-17 production and inflammation need to be explored further.KeywordsFocal Adhesion KinaseIdiopathic Pulmonary FibrosisLung InflammationiNKT CellNeutrophil RecruitmentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.