Genetic deletion of IL-17A reduces cigarette smoke-induced inflammation and alveolar type II cell apoptosis

<jats:p>Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked by relative resistance to steroids. Inflammation and apoptosis have been suggested to be important mechanisms for COPD. Interleukin (IL)-17 superfamily has been associated with chronic inflammation and diminished responses to steroids. It is reasonable to consider that IL-17 may play a role in the pathogenesis of COPD. In this study, we examined IL-17 expression in mice exposed to cigarette smoke (CS) and investigated the contribution of IL-17 to CS-induced inflammation and alveolar cell apoptosis in IL-17<jats:sup>−/−</jats:sup>mice. After exposing wild-type and IL-17<jats:sup>−/−</jats:sup>mice to mainstream CS for 4 wk, IL-17A, but not IL-17F, expression was increased in mice upon CS exposure. Neutrophil infiltration in the lungs of IL-17<jats:sup>−/−</jats:sup>mice was significantly decreased. In IL-17<jats:sup>−/−</jats:sup>mice, there is reduced expression of IL-6, macrophage inflammatory protein-2, and matrix metalloproteinase-12 compared with wild-type mice after CS exposure. The number of apoptotic type II alveolar cells was significantly increased in CS-exposed wild-type mice but not in IL-17<jats:sup>−/−</jats:sup>mice. The effect of IL-17A on type II alveolar cell apoptosis was confirmed in vitro through either addition of IL-17A or transient knockdown of IL-17A by small-interfering RNA transfection in type II alveolar cells. These findings suggest that IL-17A plays an important role in the inflammatory response to CS exposure through increased multiple inflammatory mediators. Moreover, IL-17 may also contribute to type II alveolar cell apoptosis. This study opens a new option in targeting IL-17A to modulate inflammatory response to CS and may be the bases for new therapy for COPD.</jats:p>