Published in:
Open Access 01-12-2018 | Research
IL-32γ attenuates airway fibrosis by modulating the integrin-FAK signaling pathway in fibroblasts
Published in: Respiratory Research | Issue 1/2018
Login to get accessAbstract
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-32γ (rIL-32γ). Expression of fibronectin and α-smooth muscle actin (α-SMA) was examined and the transforming growth factor (TGF)-β-related signaling pathways was evaluated in activated human lung fibroblasts (MRC-5 cells) treated with rIL-32γ.
Results
rIL-32γ significantly attenuated collagen deposition and α-SMA production in both mouse models. rIL-32γ inhibited the production of fibronectin and α-SMA in MRC-5 cells stimulated with TGF-β. Additionally, rIL-32γ suppressed activation of the integrin-FAK-paxillin signaling axis but had no effect on the Smad and non-Smad signaling pathways. rIL-32γ 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-32γ has anti-fibrotic effects and is a novel target for preventing fibrosis.