Interleukin-19 Aggravates Pulmonary Fibrosis via Activating Fibroblast through TGF- β/Smad Pathway

  • Mediators Inflamm. 2022 Mar 3:2022:6755407. doi: 10.1155/2022/6755407.
Yu Wang  1 Sibo Sun  1 Kai Wang  1 Mingjiong Zhang  1 Min Li  1 Yumin Zan  1 Qiqing Huang  1 Shuangshuang Wu  1 Weihong Zhao  1 Wei Xu  1 Jianqing Wu  1
Affiliations
  • 1. Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia disease with no cure. Communication between injured cells is triggered and maintained by a complicated network of cytokines and their receptors. IL-19 is supported by increasing evidences for a deleterious role in respiratory diseases. However, its potential role in lung fibrosis has never been explored.

Methods: Bioinformatic, immunohistochemistry and western blot analysis were used to assess the expression of IL-19 in human and mouse fibrosis lung tissues. CCK-8, transwell and flow cytometry assay were utilized to analyze the effect of IL-19 on biological behaviors of lung fibroblasts. Histopathology was used to elucidate profibrotic effect of IL-19 in vivo.

Results: IL-19 was upregulated in fibrosis lung tissues. IL-19 promoted lung fibroblasts proliferation and invasion, inhibited cell Apoptosis, and induced differentiation of fibroblasts to the myofibroblast phenotype, which could be revised by LY2109761, a TGF-β/Smad signaling pathway inhibitor. Furthermore, we found that IL-19 aggravated lung fibrosis in murine bleomycin-induced lung fibrosis.

Conclusions: Our results imply the profibrotic role for IL-19 through direct effects on lung fibroblasts and the potential of targeting IL-19 for therapeutic intervention in pulmonary fibrosis.

Products
Inhibitors & Agonists
Other Products