Pro-fibrotic effects of IL-17A and elevated IL-17RA in IPF and RA-ILD support a direct role for IL-17A/IL-17RA in human fibrotic interstitial lung disease.

Pro-fibrotic effects of IL-17A and elevated IL-17RA in IPF and RA-ILD support a direct role for IL-17A/IL-17RA in human fibrotic interstitial lung disease. Am J Physiol Lung Cell Mol Physiol. 2019 Jan 03;: Authors: Zhang J, Wang D, Wang L, Wang S, Roden AC, Zhao H, Li X, Prakash YS, Matteson EL, Tschumperlin DJ, Vassallo R Abstract Interleukin-17 (IL-17) is a T helper 17 (Th17) cytokine implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Although IL-17A has a well-established role in murine pulmonary fibrosis models, it's role in the tissue remodeling and fibrosis occurring in idiopathic pulmonary fibrosis (IPF) and RA associated interstitial lung disease (RA-ILD) is not very well defined. To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with idiopathic pulmonary fibrosis (IPF) and RA-ILD to determine IL-17RA receptor expression. Both normal and pathogenic IPF lung fibroblasts express functional IL-17A receptor (IL-17RA) and respond to IL-17A stimulation with cell proliferation, generation of extracellular matrix (ECM) proteins, and induction of myofibroblast trans-differentiation. Small interfering RNA (siRNA) silencing of IL-17RA attenuated this fibroblast response to IL-17A on ECM production. These fibroblast responses to IL-17A are dependent on ...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research