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Inflammation Research

, Volume 59, Issue 3, pp 177–188 | Cite as

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
Original Research Paper

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.

Keywords

Thalidomide Bleomycin Lung Fibrosis TGF-β ERK1/2 

Notes

Acknowledgments

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

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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Jung-Yoon Choe
    • 1
    • 2
  • Hyun-Joo Jung
    • 2
  • Ki-Yeun Park
    • 2
  • Yoon-Seup Kum
    • 3
  • Gwan Gyu Song
    • 4
  • Dae-Sung Hyun
    • 1
  • Sung-Hoon Park
    • 1
    • 2
  • Seong-Kyu Kim
    • 1
    • 2
  1. 1.Department of Internal MedicineCatholic University of Daegu School of MedicineDaeguSouth Korea
  2. 2.Arthritis and Autoimmunity Research CenterCatholic University of Daegu School of MedicineDaeguSouth Korea
  3. 3.Department of PathologyCatholic University of Daegu School of MedicineDaeguSouth Korea
  4. 4.Division of Rheumatology, College of MedicineKorea UniversitySeoulSouth Korea

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