Il-27 Inhibits The Tgf-Beta 1-Induced Epithelial-Mesenchymal Transition In Alveolar Epithelial Cells

Background: IL-27 is a multifunctional cytokine that has both pro-inflammatory and anti-inflammatory functions. Although IL-27 has been shown to potently inhibit lung fibrosis, the detailed mechanism of IL-27 in this process is poorly understood. Epithelial-mesenchymal transition (EMT) is one of the key mechanisms involved in pulmonary fibrosis. We assessed the effects of IL-27 on TGF-beta 1-induced EMT in alveolar epithelial cells.Methods: A549 cells (a human AEC cell line) were incubated with TGF-beta 1, IL-27, or both TGF-beta 1 and IL-27, and changes in E-cadherin, beta-catenin, vimentin and a-SMA levels were measured using real-time PCR, western blotting and fluorescence microscopy. The related proteins in the JAK/STAT and TGF-beta/Smad signalling pathways were examined by western blot.Results: IL-27 increased the expression of epithelial phenotypic markers, including E-cadherin and beta-catenin, and inhibited mesenchymal phenotypic markers, including vimentin and a-SMA in A549 cells. Moreover, TGF-beta 1-induced EMT was attenuated by IL-27. Furthermore, we found that TGF-beta 1 activated the phosphorylation of JAK1, STAT1, STAT3, STAT5, Smad1, Smad3 and Smad5, and IL-27 partially inhibited these changes in this process. When cells were treated with the STAT3 specific inhibitor wp1006 and the Smad3 specific inhibitor SIS3, the inhibition of EMT by IL-27 was significantly strengthened.Conclusion: Our results suggest that IL-27 attenuates epithelial-mesenchymal transition in alveolar epithelial cells in the absence or presence of TGF-beta 1 through the JAK/STAT and TGF-beta/Smad signalling pathways.