title: IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells.
abstract: 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-β1-induced EMT in alveolar epithelial cells.
  
  
  METHODS
  A549 cells (a human AEC cell line) were incubated with TGF-β1, IL-27, or both TGF-β1 and IL-27, and changes in E-cadherin, β-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-β/Smad signalling pathways were examined by western blot.
  
  
  RESULTS
  IL-27 increased the expression of epithelial phenotypic markers, including E-cadherin and β-catenin, and inhibited mesenchymal phenotypic markers, including vimentin and a-SMA in A549 cells. Moreover, TGF-β1-induced EMT was attenuated by IL-27. Furthermore, we found that TGF-β1 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.
  
  
  CONCLUSIONS
  Our results suggest that IL-27 attenuates epithelial-mesenchymal transition in alveolar epithelial cells in the absence or presence of TGF-β1 through the JAK/STAT and TGF-β/Smad signalling pathways.
authors.affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, Dianmian Road 374, Kunming, Yunnan, 650101, China. dongkm@hotmail.com.
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The 2nd Affiliated Hospital of Kunming Medical University, Dianmian Road, Kunming, Yunnan, China. 2820582685@qq.com.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Tai
authors.affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, Dianmian Road 374, Kunming, Yunnan, 650101, China. 2233851218@qq.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Lei
authors.affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, Dianmian Road 374, Kunming, Yunnan, 650101, China. w.y925@163.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, Dianmian Road 374, Kunming, Yunnan, 650101, China. ljk5718@sina.com.
authors.forename: ZhenKun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, Dianmian Road 374, Kunming, Yunnan, 650101, China. ZT6958@sina.com.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D064094:Interleukin-27 / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D064094:Interleukin-27; D050796:STAT3 Transcription Factor; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D014746:Vimentin