Hydroquinone inhibits PMA-induced activation of NF kappa B in primary human CD19(+) B lymphocytes

Citation
Dw. Pyatt et al., Hydroquinone inhibits PMA-induced activation of NF kappa B in primary human CD19(+) B lymphocytes, CELL BIOL T, 16(1), 2000, pp. 41-51
Citations number
40
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL BIOLOGY AND TOXICOLOGY
ISSN journal
07422091 → ACNP
Volume
16
Issue
1
Year of publication
2000
Pages
41 - 51
Database
ISI
SICI code
0742-2091(2000)16:1<41:HIPAON>2.0.ZU;2-R
Abstract
Hydroquinone (HQ), a reactive metabolite of benzene, is known to inhibit mi togen-stimulated activation of both T and B lymphocytes. Despite extensive study, the underlying mechanism for the immunotoxicity of the HQ is not cle ar. We have previously demonstrated that 1 mu mol/L HQ inhibits TNF-induced activation of NF kappa B in CD4(+) T cells, resulting in decreased IL-2 pr oduction. NF kappa B, known to be important in T lymphocytes, also plays a critical role in normal B cell development and activation. We therefore hyp othesized that alterations in NF kappa B might be involved in HQ-induced B cell immunosuppression as well. In this study, we demonstrate that 1-10 mu mol/L HQ inhibits PMA/ionomycin-induced activation of NF kappa B in primary human CD19(+) B cells. Inhibition of NF kappa B is accompanied by a dose-d ependent decrease in PMA-stimulated production of TNF with no corresponding loss in viability or increased apoptosis. HQ also does not appear to alter NF kappa B directly, as preincubation of B cell nuclear extracts with HQ d oes not diminish DNA binding activity of this protein. In contrast to T cel ls, inhibition of NF kappa B by HQ in B cells is not reversible after 72 h in culture, suggesting a long-term functional suppression. These data suppo rt our original findings in T cells and indicate that NF kappa B is particu larly susceptible to inhibition by HQ. We further hypothesize that inhibiti on of NF kappa B in lymphocytes, and perhaps other cell types as well, may play a significant role in the observed toxicity of HQ.