NF-κB-Independent Suppression of HIV Expression by Ascorbic Acid

Abstract

Ascorbic acid (ascorbate or vitamin C) has been shown to suppress the induction of HIV in latently infected T lymphocytic cells following stimulation with a tumor promoter (PMA) and inflammatory cytokine (TNF-α). To assess whether this inhibition was mediated via modulation of the cellular transcription factor, NF-κB, we carried out gel shift analysis on nuclear extracts prepared under different conditions of cell stimulation in the presence or absence of ascorbate, N-acetylcysteine (NAC), or zidovudine (AZT). Pretreatment of ACH-2 T cells by NAC followed by stimulation with PMA, TNF-α, or hydrogen peroxide (H2O2) resulted in strong suppression of NF-κB activation. In contrast, neither ascorbate nor AZT affected NF-κB activity under all three induction conditions in the ACH-2 cell line. Ascorbate and AZT also had no effect on NF-κB activation following TNF-α- or PMA-induced stimulation of U1 promonocytic cells. These results suggest that the molecular mechanism of HIV inhibition by ascorbate is not mediated via NF-κB inhibition, unlike that seen with other antioxidants.