Abstract
Hydroquinone (HQ), a reactive metabolite of benzene, is known to inhibit mitogen-stimulated activation of both T and B lymphocytes. Despite extensive study, the underlying mechanism for the immunotoxicity of the HQ is not clear. We have previously demonstrated that 1 μmol/L HQ inhibits TNF-induced activation of NFκB in CD4+ T cells, resulting in decreased IL-2 production. NFκB, known to be important in T lymphocytes, also plays a critical role in normal B cell development and activation. We therefore hypothesized that alterations in NFκB might be involved in HQ-induced B cell immunosuppression as well. In this study, we demonstrate that 1–10 μmol/L HQ inhibits PMA/ionomycin-induced activation of NFκB in primary human CD19+ B cells. Inhibition of NFκB is accompanied by a dose-dependent decrease in PMA-stimulated production of TNF with no corresponding loss in viability or increased apoptosis. HQ also does not appear to alter NFκB directly, as preincubation of B cell nuclear extracts with HQ does not diminish DNA binding activity of this protein. In contrast to T cells, inhibition of NFκB by HQ in B cells is not reversible after 72 h in culture, suggesting a long-term functional suppression. These data support our original findings in T cells and indicate that NFκB is particularly susceptible to inhibition by HQ. We further hypothesize that inhibition of NFκB in lymphocytes, and perhaps other cell types as well, may play a significant role in the observed toxicity of HQ.
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Pyatt, D., Yang, Y., Stillman, W. et al. Hydroquinone inhibits PMA-induced activation of NFκB in primary human CD19+ B lymphocytes. Cell Biol Toxicol 16, 41–57 (2000). https://doi.org/10.1023/A:1007644620655
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DOI: https://doi.org/10.1023/A:1007644620655