Glucocorticoid can reduce the transcriptional activation of HIV-1 promoter through the reduction of active NF-kappaB.
It is well documented that glucocorticoid (GC) can induce the transcription of the IkappaBalpha gene in several cell lines. GC treatment then increases IkappaBalpha protein levels and markedly reduces the amount of active NF-kappaB. NF-kappaB is a strong activator of HIV-1 promoter, but the mechanism by which GC influence the HIV-1 activities is not well documented. In the present study, MOLT4 and Jurkat cells were transfected with HIV-1-LTR-CAT DNA and treated with 0.2 mM H(2)O(2) or 10 ng/ml of TPA. CAT activities of the transformed MOLT4 and Jurkat cells were greatly enhanced by these treatments, but the CAT activities were markedly reduced when cells were pretreated with GC. This reduction in activity correlated well with the reduction in active NF-kappaB and the accumulation of IkappaBalpha. These findings suggest that GC can reduce the transcription of HIV-1 promoter through the reduction of active NF-kappaB.
Kurata
S i
Si
Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Tokyo 113, Japan.
Yamamoto
N
N
D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects*
D016328:NF-kappa B; D003907:Dexamethasone; D006861:Hydrogen Peroxide; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate