IL-17A-Induced Redox Imbalance and Inflammatory Responses in Mice Lung via Act1-TRAF6-IKBα Signaling Pathway: Implications for Lung Disease Pathogenesis.

Abstract

IL-17A is a potent proinflammatory cytokine that plays a crucial role in the pathogenesis of various lung diseases. This study focused on the evaluation of the role of IL-17 receptor signaling through one-week intranasal exposure of IL-17A in lung tissues of BALB/c mice. IL-17A triggered inflammatory responses in the mice lungs and led to changes in the morphological alveolar arrangements. Exposure of IL-17A induced redox imbalance by triggering an increase in the level of the pro-oxidants (reactive oxygen species, nitrite and malondialdehyde) and reduction of the levels of antioxidant proteins (glutathione, superoxide dismutase and catalase) in the lung tissue. IL-17A also caused a significant elevation in the levels of proinflammatory cytokines lines including TNF-α, IL-1β and IL-6, in lung tissue as well as in plasma. More interestingly, these changes were accompanied by the alterations in IL-17 receptor downstream signaling through activation of IL-17R-Act1-TRAF6-IKBα-mediated pathway. IL-17A exposure also caused lung tissue injury, recruitment and polarization of immune cells from anti-inflammatory to pro-inflammatory. This study clearly demonstrated the role of IL-17A-induced signaling in worsening lung inflammatory diseases, and hence points towards its emergence as an important therapeutic target to control lung inflammation.