Hydroquinone inhibits PMA-induced activation of NFkappaB in primary human CD19+ B lymphocytes.

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 micromol/L HQ inhibits TNF-induced activation of NFkappaB in CD4+ T cells, resulting in decreased IL-2 production. NFkappaB, 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 NFkappaB might be involved in HQ-induced B cell immunosuppression as well. In this study, we demonstrate that 1-10 micromol/L HQ inhibits PMA/ionomycin-induced activation of NFkappaB in primary human CD19+ B cells. Inhibition of NFkappaB 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 NFkappaB 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 NFkappaB 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 NFkappaB is particularly susceptible to inhibition by HQ. We further hypothesize that inhibition of NFkappaB in lymphocytes, and perhaps other cell types as well, may play a significant role in the observed toxicity of HQ.