Activation of toll-like receptor 3 augments myofibroblast differentiation

Hisatoshi Sugiura, Tomohiro Ichikawa, Akira Koarai, Satoru Yanagisawa, Yoshiaki Minakata, Kazuto Matsunaga, Tsunahiko Hirano, Keiichiro Akamatsu, Masakazu Ichinose

研究成果: Article査読

50 被引用数 (Scopus)

抄録

Airway remodeling is observed in the airways of patients with asthma, and differentiation of fibroblasts to myofibroblasts plays a critical role in the progress of airway remodeling. Viral infection induces not only the disease development and exacerbations but also airway remodeling. The aim of this study was to evaluate whether the activation of Toll-like receptor 3 (TLR3) can affect the differentiation of fibroblasts to myofibroblasts and the extracellular matrix(ECM)protein production.Humanfetal lung fibroblasts (HFL-1) and adult lung fibroblasts were treated with a synthetic double-stranded RNA, polyinosine-polycytidylic acid (poly[I:C]) and the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation, was evaluated. The release of transforming growth factor-β1 (TGF-β1) and ECM protein production were assessed. The effect of anti-TGF-β antibody on the α-SMA and ECM production was also assessed. Poly(I:C) significantly augmented the α-SMA expression (P < 0.01) and release of TGF-β1 (P < 0.01) compared with control. Bafilomycin, an inhibitor of TLR3 signaling, diminished poly(I:C)-augmented TGF-β1 release. Anti-TGF-β1 antibody inhibited the poly(I:C)-augmented α-SMA expression. Poly(I:C) enhanced translocation of nuclear factor-κB (NF-κB) and interferon regulatory factor-3 (IRF-3) into the nucleus. Poly(I:C)-augmented TGF-β1 release was almost completely blocked by NF-κB inhibitors, but not by silencing IRF-3. The production of fibronectin and collagen I expression were significantly increased by poly(I:C) (P < 0.01) and they were inhibited by anti-TGF-β antibody. These results suggest that activation of TLR3 can affect the differentiation to myofibroblasts and enhance ECM production via the NF-κB-TGF-β1-dependent pathway.

本文言語English
ページ(範囲)654-662
ページ数9
ジャーナルAmerican journal of respiratory cell and molecular biology
40
6
DOI
出版ステータスPublished - 2009 6 1
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 呼吸器内科
  • 臨床生化学
  • 細胞生物学

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