Hydroquinone inhibits PMA-induced activation of NFκB in primary human CD19+ B lymphocytes
Hydroquinone inhibits PMA-induced activation of NFκB in primary human CD19+ B lymphocytes
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DOI：
10.1023/a:1007644620655
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发表时间：
2000-01-01
影响因子：
6.1
通讯作者：
Irons, RD
中科院分区：
文献类型：
--
作者：
Pyatt, DW;Yang, Y;Irons, RD
对苯二酚（HQ）是苯的反应性代谢产物，已知可抑制T和B淋巴细胞的有丝分裂原刺激活化。尽管进行了广泛的研究，但HQ免疫毒性的潜在机制尚不清楚。我们以前已经证明，1 μ mol/L HQ抑制TNF诱导的CD 4（+）T细胞中NF κ B B的活化，导致IL-2产生减少。已知NF kappa B在T淋巴细胞中很重要，也在正常B细胞发育和激活中发挥关键作用。因此，我们推测NF κ B B的改变可能也参与了HQ诱导的B细胞免疫抑制。在这项研究中，我们证明1-10 μ mol/L HQ抑制PMA/离子霉素诱导的原代人CD 19（+）B细胞中NF κ B的活化。NF κ B的抑制伴随着PMA刺激的TNF产生的剂量依赖性降低，而没有相应的活力损失或凋亡增加。HQ似乎也不会直接改变NF κ B B，因为用HQ预孵育B细胞核提取物不会降低该蛋白的DNA结合活性。与T细胞相反，在B细胞中HQ对NF κ B B的抑制在培养72小时后是不可逆的，这表明了长期的功能抑制。这些数据支持我们在T细胞中的原始发现，并表明NF κ B对HQ的抑制特别敏感。我们进一步假设，抑制淋巴细胞中的NF κ B B，也许还有其他细胞类型，可能在观察到的HQ毒性中起重要作用。
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 mu mol/L HQ inhibits TNF-induced activation of NF kappa B in CD4(+) T cells, resulting in decreased IL-2 production. NF kappa B, 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 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-dependent 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 does not diminish DNA binding activity of this protein. In contrast to T cells, 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 support our original findings in T cells and indicate that NF kappa B is particularly susceptible to inhibition by HQ. We further hypothesize that inhibition of NF kappa B in lymphocytes, and perhaps other cell types as well, may play a significant role in the observed toxicity of HQ.