Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats.

Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats.
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DOI:
10.1002/jat.2866
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发表时间:
2014-03
影响因子:
3.3
通讯作者:
Wang, Jia-Sheng
Wang, Jia-Sheng
中科院分区:
医学4区
文献类型:
--
作者:
Qian, Guoqing;Tang, Lili;Guo, Xia;Wang, Franklin;Massey, Michael E.;Su, Jianjia;Guo, Tai L.;Williams, Jonathan H.;Phillips, Timothy D.;Wang, Jia-Sheng

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黄曲霉毒素B1(AFB 1)对动物有免疫毒性,对人类可能有免疫抑制作用。本研究观察了黄曲霉毒素B1对雄性F344大鼠脾淋巴细胞表型和炎性细胞因子表达的影响。动物暴露于AFB 1(5-75 μg/kg体重)1周后,脾脏CD 8 + T细胞和CD 3 − CD 8a + NK细胞的百分比呈剂量依赖性下降。还发现CD 4 + T细胞的IL-4和IFN-γ表达、CD 8a+细胞的IL-4和IFN-γ表达以及NK细胞的TNF-α表达普遍受到抑制;然而,脾组织中不存在并发的组织学变化,表明急性免疫抑制无明显毒性。5周的AFB 1暴露显著增加了CD 3+和CD 8 + T细胞的百分比,特别是在低剂量(≤ 25 μg/kg)时。AFB 1处理显著降低CD 4 + T细胞表达抗炎细胞因子IL-4,显著增加CD 4 + T细胞表达促炎细胞因子IFN-γ和NK细胞表达TNF-α。这些结果表明,重复的AFB 1暴露通过调节细胞因子的表达促进炎症反应。我们的数据提供了新的见解AFB 1暴露差异调节细胞介导的免疫反应的机制,并表明在重复暴露后的炎症反应的参与。
Aflatoxin B1 (AFB1) is immunotoxic to animals and a suspected immunosuppressant in humans. In this study, we investigated the effects of AFB1 on splenic lymphocyte phenotypes and the inflammatory cytokine expression in male F344 rats. Exposure of animals to AFB1 (5-75 μg/kg body weight) for 1-week showed dose-dependent decreases in the percentage of splenic CD8+ T cells and CD3−CD8a+ NK cells. A general inhibition of the expression of IL-4 and IFN-γ by CD4+ T cells, IL-4 and IFN-γ by CD8a+ cells, and TNF-α expression by NK cells was also found; however, no concurrent histological changes in spleen tissue were present, suggesting acute immunosuppression without overt toxicity. Five-week exposure with AFB1 significantly increased the percentages of CD3+ and CD8+ T cells, especially at low doses (≤ 25 μg/kg). AFB1 treatment significantly decreased the anti-inflammatory cytokine IL-4 expression by CD4+ T cells and significantly increased the pro-inflammatory cytokine IFN-γ expression by CD4+ T cells and TNF-α expression by NK cells. These results indicated that repeated AFB1 exposure promotes inflammatory responses by regulating cytokine expression. Our data provides novel insights into the mechanisms by which AFB1 exposure differentially modulates the cell-mediated immune responses and suggests the involvement of an inflammatory response upon repeated exposure.
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