Glucocorticoids modulate TGF-β production

Fu Qiang Wen, Tadashi Kohyama, C. Magnus Sköld, Yun Kiu Zhu, Xiang-de Liu, Debra Romberger, Julie Stoner, Stephen I. Rennard

Research output: Contribution to journalArticle

24 Scopus citations

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-β, -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.

Original languageEnglish (US)
Pages (from-to)279-290
Number of pages12
JournalInflammation
Volume26
Issue number6
DOIs
StatePublished - Dec 1 2002

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Keywords

  • AP-1 complex
  • Fibroblast
  • Glucocorticoids
  • Smads
  • Transforming growth factor-β (TGF-β)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Wen, F. Q., Kohyama, T., Sköld, C. M., Zhu, Y. K., Liu, X., Romberger, D., Stoner, J., & Rennard, S. I. (2002). Glucocorticoids modulate TGF-β production. Inflammation, 26(6), 279-290. https://doi.org/10.1023/A:1021412601538