Regulatory effect of cytokines on promoter activity of human transforming growth factor-?_1 gene / 中国免疫学杂志

ABSTRACT

Objective:To study the effect of the cytokines, tumor necrosis factor-?(TNF-?), interferon-?(IFN-?), interferon-?(IFN-?), platelet-derived growth factor BB(PDGF-BB), basic fibroblast growth factor(bFGF),on promoter activity of human transforming growth factor-?1(TGF-?1) gene.Methods:A construct of phTGF2.14 containing sequence from -1 328 bp to +812 bp of human TGF-?1 gene,linking with chloramphenicol acetyltransferase(CAT) as reporter gene,was transiently transfected into rat hepatic stellate cell line nFSC. The cells were subsequently treated with TNF-?,IFN-?,IFN-?,PDGF-BB,bFGF, and the CAT activity was assessed 48 hours after stimulation with each cytokines.Results:TNF-? of 10 ng/ml can increased the CAT activity of phTGF2.14 to 3.24 fold compared to control. IFN-? and IFN-? at 1 000 U/ml decreased CAT activity to (42?12)% and (58?6)% of control respectively.PDGF-BB,bFGF of 10 ng/ml had no effect on promoter activity of human TGF-?1 gene;Combined application of IFN-?,IFN-? and TNF-?,the promoter TGF-?1 gene were 1.32 and 1.46 fold compared with control,respectively.Conclusion:These data indicate that TNF-? can increase the promoter activity of human TGF-?1 gene, but IFN-?,IFN? can downregulate the CAT activites of phTGF2.14, and IFN-?,IFN-? can interdict the upregulate effect of TNF-? on phTGF2.14. We did not find PDGF-BB,bFGF have any effect on TGF-?1 promoter. These provided an essential evidence for study the interaction mechanism of cytokines in fibrogenisis diseases.