Glucocorticoids modulate TGF-beta production.

Abstract

TGF-beta 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-beta isoforms affect TGF-beta 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-beta1, -beta2, and -beta3. TGF-beta 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-beta2 and -beta3 stimulated TGF-beta1 production significantly (p < 0.01 relative to control). TGF-beta1 stimulated TGF-beta2 production (p < 0.01 relative to control). TGF-beta3 was undetectable. Glucocorticoids significantly inhibited TGF-beta1 and -beta2 production and reduced expression of the upregulated TGF-beta1 and -beta2 mRNA induced by exogenous TGF-beta1, -beta2 or -beta3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF-beta-stimulated cells, it was reduced by glucocorticoids. Thus, TGF-beta isoforms may stimulate production of various TGF-beta isoforms in the lung. Glucocorticoids then may block TGF-beta production by modulating mRNA levels and c-Jun.

• Authors: Fu-Qiang Wen, Tadashi Kohyama, C Magnus Sköld, Yun Kiu Zhu, Xiangde Liu, Debra J Romberger, Julie Stoner, Stephen I Rennard
• Journal: Inflammation (Inflammation) Vol. 26 Issue 6 Pg. 279-90 (Dec 2002) ISSN: 0360-3997 [Print] United States
• PMID: 12546137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glucocorticoids
• Protein Isoforms
• Transforming Growth Factor beta

Topics

• Animals
• Dose-Response Relationship, Drug
• Fetus
• Fibroblasts (cytology, drug effects, metabolism)
• Glucocorticoids (pharmacology)
• Humans
• Lung (cytology, drug effects, metabolism)
• Mice
• Protein Isoforms (biosynthesis, pharmacology)
• Transforming Growth Factor beta (biosynthesis, pharmacology)