Skip Navigation

Publication Detail

Title: Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

Authors: Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

Published In J Pharmacol Exp Ther, (1998 Dec)

Abstract: Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

PubMed ID: 9864299 Exiting the NIEHS site

MeSH Terms: Animals; DNA-Binding Proteins/biosynthesis*; Gene Expression/drug effects; Interleukin-2/biosynthesis*; Interleukin-2/genetics; Mice; Mice, Inbred C57BL; NF-kappa B/biosynthesis*; NFATC Transcription Factors; Nuclear Proteins*; RNA, Messenger/biosynthesis; Research Support, U.S. Gov't, P.H.S.; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcription Factor AP-1/biosynthesis*; Transcription Factors/biosynthesis*; Transcription, Genetic; Transforming Growth Factor beta/pharmacology*; Tumor Cells, Cultured; Up-Regulation

Back
to Top