PMID- 1939646 OWN - NLM STAT- MEDLINE DCOM- 19911213 LR - 20181113 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 88 IP - 5 DP - 1991 Nov TI - Regulation of transforming growth factor-beta 1 gene expression by glucocorticoids in normal human T lymphocytes. PG - 1574-80 AB - 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. FAU - AyanlarBatuman, O AU - AyanlarBatuman O AD - Cardeza Foundation for Hematologic Research, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107. FAU - Ferrero, A P AU - Ferrero AP FAU - Diaz, A AU - Diaz A FAU - Jimenez, S A AU - Jimenez SA LA - eng GR - AM 19101/AM/NIADDK NIH HHS/United States GR - HL41214/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Transforming Growth Factor beta) RN - 7S5I7G3JQL (Dexamethasone) RN - 98600C0908 (Cycloheximide) SB - IM MH - Cells, Cultured MH - Cycloheximide/pharmacology MH - Dexamethasone/*pharmacology MH - Gene Expression Regulation/*drug effects MH - Humans MH - Lymphocyte Activation MH - T-Lymphocytes/*metabolism MH - Transcription, Genetic/drug effects MH - Transforming Growth Factor beta/biosynthesis/*genetics PMC - PMC295675 EDAT- 1991/11/01 00:00 MHDA- 1991/11/01 00:01 PMCR- 1991/11/01 CRDT- 1991/11/01 00:00 PHST- 1991/11/01 00:00 [pubmed] PHST- 1991/11/01 00:01 [medline] PHST- 1991/11/01 00:00 [entrez] PHST- 1991/11/01 00:00 [pmc-release] AID - 10.1172/JCI115469 [doi] PST - ppublish SO - J Clin Invest. 1991 Nov;88(5):1574-80. doi: 10.1172/JCI115469.