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Glucocorticoids modulate TGF-beta production.

Fu-Qiang Wen·Tadashi Kohyama·C Magnus Sköld·Yun Kiu Zhu·Xiangde Liu·Debra J Romberger·Julie Stoner·Stephen I Rennard
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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.

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AnimalsDose-Response Relationship, DrugFetusFibroblastsGlucocorticoidsHumansLungMiceProtein IsoformsTransforming Growth Factor betaJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Fu-Qiang Wen, Tadashi Kohyama, C Magnus Sköld, Yun Kiu Zhu, Xiangde Liu, Debra J Romberger, Julie Stoner, Stephen I Rennard. 2002. Glucocorticoids modulate TGF-beta production.. https://doi.org/10.1023/a%3A1021412601538

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