Glucocorticoids modulate TGF-β production by human fetal lung fibroblasts

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

32 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 TGF-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 (HFLF) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TGF-β1, -β2, or -β3. Post-culture media were collected for ELISA assays of TGF-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. TFG-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 TGF-β2 production and reduced expression of the up-regulated TGF-β1 and TGF-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)9-19
Number of pages11
JournalInflammation
Volume27
Issue number1
DOIs
Publication statusPublished - Feb 1 2003

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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

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