| 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.
This revised version was published online in July 2006 with corrections to the Cover Date. |
