IL-32γ attenuates airway fibrosis by modulating the integrin-FAK signaling pathway in fibroblasts

초록

Background: Fibrosis in severe asthma often leads to irreversible organ dysfunction. However, the mechanism that regulates fibrosis remains poorly understood. Interleukin (IL)-32 plays a role in several chronic inflammatory diseases, including severe asthma. In this study, we investigated whether IL-32 is involved in fibrosis progression in the lungs. Methods: Murine models of chronic airway inflammation induced by ovalbumin and Aspergillus melleus protease and bleomycin-induced pulmonary fibrosis were employed. We evaluated the degree of tissue fibrosis after treatment with recombinant IL-32 gamma (rIL-32 gamma). Expression of fibronectin and alpha-smooth muscle actin (alpha-SMA) was examined and the transforming growth factor (TGF)-beta-related signaling pathways was evaluated in activated human lung fibroblasts (MRC-5 cells) treated with rIL-32 gamma. Results: rIL-32 gamma significantly attenuated collagen deposition and alpha-SMA production in both mouse models. rIL-32 gamma inhibited the production of fibronectin and alpha-SMA in MRC-5 cells stimulated with TGF-beta. Additionally, rIL-32 gamma suppressed activation of the integrin-FAK-paxillin signaling axis but had no effect on the Smad and non-Smad signaling pathways. rIL-32 gamma localized outside of MRC-5 cells and inhibited the interaction between integrins and the extracellular matrix without directly binding to intracellular FAK and paxillin. Conclusions: These results demonstrate that IL-32 gamma has anti-fibrotic effects and is a novel target for preventing fibrosis.

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