Selective inhibition of IL-2 gene expression by trichostatin A, a potent inhibitor of mammalian histone deacetylase.
During screening for inhibitors of T cell activation, we have found that trichostatin A (TSA), known as a potent inhibitor of histone deacetylase, showed selective inhibitory activity against IL-2 gene expression. From luciferase reporter experiments on human leukemic Jurkat T cells, TSA was found to inhibit the expression of the luciferase reporter gene directed by the IL-2 enhancer and promoter with a 50% inhibitory concentration value of 0.073 microM. On the other hand, TSA, at the same concentration, enhanced the expression of the luciferase reporter gene directed by the c-fos enhancer and promoter. The result of RT-PCR experiments also indicates that TSA has selective inhibitory activity against IL-2 gene expression in Jurkat cells. These results suggest that the change in chromatin structure caused by the hyperacetylation of histone might affect the regulation of IL-2 and c-fos gene expression.
Takahashi
I
I
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Miyaji
H
H
Yoshida
T
T
Sato
S
S
Mizukami
T
T
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007376:Interleukin-2; C012589:trichostatin A