Iron Chelation Decreases NF- k 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 kB (NF-kB) 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-kB 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-kB activation as well as TNF-α-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 μM. Other chemically unrelated iron chelators also provided protection against cytotoxicity, NF-kB activation, and HIV-1 activation in U1 cells challenged with H₂O₂.