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A Role of IL‐21 in Pulmonary Fibroblast Activation
Author(s) -
Sathiaseelan Roshini,
Huang Chaoqun,
Senavirathna Lakmini Kumari,
Liu Lin
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.656.15
Subject(s) - fibroblast , myofibroblast , pulmonary fibrosis , idiopathic pulmonary fibrosis , transforming growth factor , fibrosis , extracellular matrix , lung , biology , cancer research , immunology , chemistry , microbiology and biotechnology , medicine , pathology , cell culture , genetics
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial fibrotic lung disease with a poor prognosis. Activated fibroblasts produce excess extracellular matrix leading to fibrosis. Transforming growth factor β (TGFβ) is increased in IPF and is one of the most important factors for the activation of fibroblasts. T lymphocytes‐derived cytokines such as IL‐13 and IL‐4 is known to stimulate macrophages to secrete TGFβ. However, the direct effects of these cytokines on the activation of fibroblasts are poorly understood. In this study, we investigated the role of IL‐21 in pulmonary fibroblast activation. RNA sequencing analysis revealed that TGFβ1 increased the expression of IL‐21 receptor (IL‐21R) in primary human pulmonary fibroblasts (HPF). The up‐regulation of IL‐21R was confirmed by real‐time PCR in normal pulmonary fibroblasts (HPF, CCD13, CCD8) and IPF fibroblasts (LL97A and LL29). To determine the effects of IL‐21 on the fibroblast functions, pulmonary fibroblasts were serum‐starved for 16 hours and then treated with TGFβ1 and/or recombinant human IL‐21 for 2 days. The mRNA expression of myofibroblast marker, α‐smooth muscle actin was markedly increased by TGFβ and IL‐21 in all of the fibroblast cell lines. We conclude that IL‐21 promotes the differentiation of fibroblasts to myofibroblasts via TGFβ‐induced IL‐21R expression. Support or Funding Information R01HL116876 and P20GM103648