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Glucocorticoids Modulate TGF-β Production

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Abstract

TGF-β is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGB-β isoforms affect TGF-β production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFL-1) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TFG-β1, -β2, and -β3. TGF-β mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TGF-β2 and -β3 stimulated TGF-β1 production significantly (p < 0.01 relative to control). TGF-β1 stimulated TGF-β2 production (p < 0.01 relative to control). TGF-β3 was undetectable. Glucocorticoids significantly inhibited TGF-β1 and -β2 production and reduced expression of the upregulated TGF-β1 and -β2 mRNA induced by exogenous TGF-β1, -β2 or -β3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF-β-stimulated cells, it was reduced by glucocorticoids. Thus, TGF-β isoforms may stimulate production of various TGF-β isoforms in the lung. Glucocorticoids then may block TGF-β production by modulating mRNA levels and c-Jun.

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Authors and Affiliations

  1. Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska

    Fu-Qiang Wen, Tadashi Kohyama, Xiangde Liu, Debra J. Romberger & Stephen I. Rennard

  2. Department of Medicine, Karolinska Institute, Stockholm, Sweden

    C. Magnus Sköld

  3. Department of Respiratory Diseases, Jincheng Hospital, Lanzhou, China

    Yun Kiu Zhu

  4. Preventive and Societal Medicine Section, University of Nebraska Medical Center, Omaha, Nebraska

    Julie Stoner

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  1. Fu-Qiang Wen
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  2. Tadashi Kohyama
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  4. Yun Kiu Zhu
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  8. Stephen I. Rennard
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Wen, FQ., Kohyama, T., Sköld, C.M. et al. Glucocorticoids Modulate TGF-β Production. Inflammation 26, 279–290 (2002). https://doi.org/10.1023/A:1021412601538

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