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

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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.

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Acknowledgments

This work was supported by the grant of Research Institute of Medical Science, Catholic University of Daegu (2008).

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Authors and Affiliations

  1. Department of Internal Medicine, Catholic University of Daegu School of Medicine, 3056-6 Daemyung 4-Dong, Namgu, Daegu, 705-718, South Korea

    Jung-Yoon Choe, Dae-Sung Hyun, Sung-Hoon Park & Seong-Kyu Kim

  2. Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, South Korea

    Jung-Yoon Choe, Hyun-Joo Jung, Ki-Yeun Park, Sung-Hoon Park & Seong-Kyu Kim

  3. Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, South Korea

    Yoon-Seup Kum

  4. Division of Rheumatology, College of Medicine, Korea University, Seoul, South Korea

    Gwan Gyu Song

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  1. Jung-Yoon Choe
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  2. Hyun-Joo Jung
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Correspondence to Seong-Kyu Kim.

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Responsible Editor: M. Parnham.

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Choe, JY., Jung, HJ., Park, KY. et al. Anti-fibrotic effect of thalidomide through inhibiting TGF-β-induced ERK1/2 pathways in bleomycin-induced lung fibrosis in mice. Inflamm. Res. 59, 177–188 (2010). https://doi.org/10.1007/s00011-009-0084-9

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  • DOI: https://doi.org/10.1007/s00011-009-0084-9

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