Hydroquinone, a Reactive Metabolite of Benzene, Inhibits NF-κB in Primary Human CD4+T Lymphocytes

Abstract

Hydroquinone (HQ), a reactive metabolite of benzene, is present in cigarette smoke and is known to inhibit mitogen-stimulated activation of both T and B lymphocytes. Despite extensive study, the underlying mechanism for HQ's immunotoxicity is not clear. NF-κB is a transcription factor known to regulate the expression of a number of genes critical for normal T cell activation. We therefore hypothesized that NF-κB might be involved in HQ-induced immunosuppression. In this study, we demonstrate that 1 μM HQ inhibits tumor necrosis factor α induced activation of NF-κB in primary human CD4+T cells. This inhibition is not accompanied by a loss in viability, and HQ-treated T cells maintain other active signaling pathways throughout the exposure duration. Additionally, the inhibition of NF-κB is reversible as HQ-treated T cells regain normal functioning after 72 h in culture. HQ does not appear to alter NF-κB directly as preincubation of nuclear extracts with HQ does not diminish activity of this protein. We further demonstrate that 1 μM HQ inhibits intracellular IL-2 production in T cells stimulated with phorbol ester but does not alter surface expression of CD25 (the α-subunit of the IL-2 receptor). These data suggest that NF-κB may be an important molecular mediator of HQ's (and benzene's) immunotoxicity.