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

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    38 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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