Regulation of transforming growth factor-beta 1 gene expression by glucocorticoids in normal human T lymphocytes.

Authors

O. AyanlarBatuman, Thomas Jefferson University
A. P. Ferrero, Thomas Jefferson University
Arturo Diaz, Thomas Jefferson UniversityFollow
Sergio A. Jimenez, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

11-1-1991

Comments

This article has been peer reviewed. It is the author’s final published version in Journal of Clinical Investigation

Volume 88, Issue 5, November 1991, Pages 1574-80.

The published version is available at DOI: 10.1172/JCI115469. Copyright © The American Society for Clinical Investigation, Inc.

Abstract

Glucocorticoids (GC) modulate immune function in a number of ways, including suppression of T cell proliferation and other IL-2-mediated T cell functions. These inhibitory effects are similar to those induced by transforming growth factor-beta 1 (TGF-beta 1), a cytokine with potent T cell inhibiting activities. We examined the hypothesis that GC effects may be at least partially achieved through modulation of the expression of the TGF-beta 1 gene in activated T cells. Normal T cells were cultured with or without purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12-myristate 13-acetate (PMA) in the presence or absence of the synthetic GC, dexamethasone (100-200 micrograms/ml). The production of latent and active forms of TGF beta by these cells were analyzed by immunoblotting and bioassays. The steady-state levels of TGF-beta 1 mRNA were analyzed in total RNA from these cells by Northern hybridizations using a human TGF-beta 1 cDNA. The results showed that dexamethasone caused an increase in TGF beta production and a dose-dependent two to fourfold increase in TGF-beta 1 mRNA in activated as well as in unstimulated T cells, 1 h after exposure of the cultures to the steroid. The increase in TGF-beta 1 mRNA levels by dexamethasone was further potentiated two to threefold by cycloheximide, suggesting that the steroid effect may be due to inhibition of the synthesis of proteins that decrease TGF-beta 1 gene transcription or the stability of its transcripts. Finally, in vitro nuclear transcription studies indicated the dexamethasone effects on TGF-beta 1 gene expression to be largely transcriptional.

Recommended Citation

AyanlarBatuman, O.; Ferrero, A. P.; Diaz, Arturo; and Jimenez, Sergio A., "Regulation of transforming growth factor-beta 1 gene expression by glucocorticoids in normal human T lymphocytes." (1991). Department of Medicine Faculty Papers. Paper 193.
https://jdc.jefferson.edu/medfp/193

PubMed ID

1939646