PT  - JOURNAL ARTICLE
AU  - Seung H. Han
AU  - Sung Su Yea
AU  - Young J. Jeon
AU  - Kyu-H. Yang
AU  - Norbert E. Kaminski
TI  - Transforming Growth Factor-<em>Beta</em> 1 (TGF-β1) Promotes IL-2 mRNA Expression Through the Up-regulation of NF-κB, AP-1 and NF-AT in EL4 Cells
DP  - 1998 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1105--1112
VI  - 287
IP  - 3
4099  - http://jpet.aspetjournals.org/content/287/3/1105.short
4100  - http://jpet.aspetjournals.org/content/287/3/1105.full
SO  - J Pharmacol Exp Ther1998 Dec 01; 287
AB  - Transforming growth factor β1 (TGF-β1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-β1 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-β1 (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-β1 on the activity of nuclear factor AT (NF-AT), nuclear factor κB (NF-κB), 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-β1 markedly increased NF-AT, NF-κB 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-κB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-β1 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-β1, 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-κB and AP-1, to help promote IL-2 mRNA expression by EL4 cells. The American Society for Pharmacology and Experimental Therapeutics