Selenium-mediated inhibition of transcription factor NF-κ B and HIV-1 LTR promoter activity

Abstract

 The eukaryotic transcription factor NF-κB is involved in the inducible expression of various inflammatory genes as well as in HIV-1 replication. Activation of NF-κB is induced by prooxidants and several stimuli eliciting oxidative stress, such as cytokines, lipopolysaccharide, UV irradiation and other mediators. Various antioxidants inhibit NF-κB activation in response to these stimuli. In this study, we have investigated the effects of selenium, an integral component of glutathione peroxidase (GPX), on NF-κB activation. In selenium-deprived Jurkat and ESb-L T lymphocytes, supplementation of selenium led to a substantial increase of GPX activity. Analysis of DNA binding revealed that NF-κB activation in response to TNF was significantly inhibited under these conditions. Likewise, reporter gene assays using luciferase constructs driven by the HIV-1 long terminal repeat showed a dose-dependent inhibition of NF-κB controlled gene expression by selenium. The effects of selenium were specific for NF-κB, since the activity of the transcription factor AP-1 was not suppressed. These data suggest that selenium supplementation may be used to modulate the expression of NF-κB target genes and HIV-1.