IRON CHELATION DECREASES NF-KAPPA-B AND HIV TYPE-1 ACTIVATION DUE TO OXIDATIVE STRESS

An important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) through redox-controlled signal transduction pathways, In this study, we demonstrate that iron chelation by deferoxamine (DFO) protects against the cytotoxic and reactivating effects of hydrogen peroxide (H2O2), These protective effects were observed both in lymphocytic (ACH-2) and promonocytic (U1) cells latently infected by HIV-1. Concomitantly, NF-kappa B activation by H2O2, when followed by gel retardation assay, was decreased in the DFO-treated U1 and ACH-2 cells, This latter DFO-mediated effect was specific, as DFO did not clearly affect AP-1 DNA-binding activity when studied after H2O2-induced stress, More importantly, DFO protected against the H2O2-induced activation of HIV-1 as evidenced by reverse transcriptase activity in the supernatant, DFO also protected against PMA-induced NF-kappa B activation as well as TNF-alpha-induced HIV-1 activation, Furthermore, DFO attenuated the p24 response in PBMC infected with HIV-1 and stimulated with IL-2, These different effects of DFO were obtained at DFO concentrations lower than 5 mu M. Other chemically unrelated iron chelators also provided protection against cytotoxicity, NF-kappa B activation, and HIV-1 activation in U1 cells challenged with H2O2.