Anti-fibrotic effect of thalidomide through inhibiting TGF-β-induced ERK1/2 pathways in bleomycin-induced lung fibrosis in mice

Jung Yoon Choe, Hyun Joo Jung, Ki Yeun Park, Yoon Seup Kum, Gwan Gyu Song, Dae Sung Hyun, Sung Hoon Park, Seong Kyu Kim

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objectives: This study is designed to confirm the anti-fibrotic effect of thalidomide on bleomycin-induced lung fibrosis in a mouse model and to identify whether this anti-fibrotic effect is associated with inhibition of the transforming growth factor-β (TGF-β)-induced extracellular signal-regulated kinase1/2 (ERK1/2). Methods and materials: C57BL/6 female mice were administered blomycin sulfate. In cultured human lung fibroblasts, expressions of type I collagen, fibronectin, and either TGF-β or IL-6 were measured after thalidomide treatment by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of ERK1/2, type I collagen, fibronectin, and TGF-β1 from lung tissues of blomycin-induced mice and from mouse lung fibroblasts were evaluated using RT-PCR and western blotting. Results: Thalidomide administration significantly inhibits TGF-β1 mRNA expression in a dose-dependant manner following administration of IL-6 and IL-6R. In the analysis of BAL fluids, total BAL inflammatory cell counts, TGF-β1, and IL-6 levels in thalidomide-treated mice were significantly reduced when compared with bleomycin-treated mice (p < 0.01, p < 0.01, and p < 0.001, respectively). Thalidomide inhibited total ERK1/2 and phospho-ERK1/2 expression after TGF-β1 stimulation in the RT-PCR and western blotting. Conclusion: The results of our study suggest that the anti-fibrotic effect of thalidomide on lung fibrosis may be related to suppression of the TGF-β1-induced ERK1/2 signaling pathway.

Original languageEnglish
Pages (from-to)177-188
Number of pages12
JournalInflammation Research
Volume59
Issue number3
DOIs
Publication statusPublished - 2010 Mar

Keywords

  • Bleomycin
  • ERK1/2
  • Fibrosis
  • Lung
  • TGF-β
  • Thalidomide

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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