SELENIUM-MEDIATED INHIBITION OF TRANSCRIPTION FACTOR NF-KAPPA-B AND HIV-1 LTR PROMOTER ACTIVITY

The eukaryotic transcription factor NF-kappa B is involved in the indu cible expression of various inflammatory genes as well as in HIV-1 rep lication. Activation of NF-kappa B is induced by prooxidants and sever al stimuli eliciting oxidative stress, such as cytokines, lipopolysacc haride, UV irradiation and other mediators. Various antioxidants inhib it NF-kappa B 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-kappa B activation. In selenium-d eprived Jurkat and ESb-L T lymphocytes, supplementation of selenium le d to a substantial increase of GPX activity. Analysis of DNA binding r evealed that NF-kappa B activation in response to TNF was significantl y inhibited under these conditions. Likewise, reporter gene assays usi ng luciferase constructs driven by the HIV-1 long terminal repeat show ed a dose-dependent inhibition of NF-kappa B controlled gene expressio n by selenium. The effects of selenium were specific for NF-KB. since the activity of the transcription factor AP-I was not suppressed. Thes e data suggest that selenium supplementation may be used to modulate t he expression of NF-kappa B target genes and HIV-1.