Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model.
Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model.
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在人巨噬细胞模型中，脱氧雪腐镰刀菌烯醇（呕吐毒素）和其他 8-酮单端孢菌素对 TNF-α、IL-6 和 IL-8 产生的差异上调。
DOI：
10.1080/152873901753246223
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Pestka,JJ
中科院分区：
文献类型：
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作者：
Sugita-Konishi,Y;Pestka,JJ
在克隆型人巨噬细胞模型中，研究了脱氧雪腐镰刀菌醇（DON或呕吐毒素）和4种密切相关的8-酮菌素对促炎细胞因子和趋化因子产生的影响。U-937细胞是人单核细胞样组织细胞淋巴瘤，经12-肉豆肉酸13-乙酸phorbol （PMA）预孵育分化为巨噬细胞。分化后的巨噬细胞在不存在或不存在脂多糖（LPS）的情况下用DON孵育，用酶联免疫吸附法（ELISA）分析上清中促炎细胞因子白介素-6 （IL-6）和肿瘤坏死因子- f （TNF- f）以及趋化因子白介素-8 （IL-8）的含量。在不存在LPS的情况下，500或1000 ng/ml的DON在3小时至6小时内上调TNF- f的产生，而100至1000 ng/ml的DON在3至24小时内显著增加IL-6的产生，在6至48小时内显著增加IL-8的产生。在0.2 μ g/ml LPS共刺激的细胞中，500或1000 ng/ml的DON显著超诱导TNF- f和IL-8的产生。虽然100 ng/ml的DON也增强了lps诱导的IL-6产生，500或1000 ng/ml的DON抑制了lps诱导的IL-6反应。另外四种8-酮赤霉素，fusarenon X, nivalenol， 3-acetyl DON和15-acetyl DON，也能够在与DON相似的浓度下上调或抑制TNF- f， IL-6和IL-8的产生。总之，结果表明，DON和其他8-酮毛菌烯具有直接诱导和超诱导人巨噬细胞中促炎细胞因子和趋化因子表达的潜力，即使毒素浓度具有细胞毒性。
The effects of deoxynivalenol (DON or vomitoxin) and four closely related 8-ketotrichothecenes on proinflammatory cytokine and chemokine production were evaluated in a clonal human macrophage model. U-937 cells, which represent a human monocytelike histocytic lymphoma, were differentiated into macrophages by preincubation with phorbol 12-myristate 13-acetate (PMA). Differentiated macrophages were incubated with DON in the absence or presence of lipopolysaccharide (LPS), and supernatant was analyzed by enzyme-linked immunosorbent assay (ELISA) for the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor- f (TNF- f ), and for the chemokine interleukin-8 (IL-8). In the absence of LPS, DON at 500 or 1000 ng/ml upregulated TNF- f production as early as 3 h and up to 6 h, whereas 100 to 1000 ng/ml of DON significantly increased production of IL-6 from 3 to 24 h and IL-8 from 6 to 48 h. In cells costimulated with 0.2 µg/ml LPS, DON at 500 or 1000 ng/ml markedly superinduced TNF- f and IL-8 production. Although 100 ng/ml of DON also potentiated LPS-induced IL-6 production, 500 or 1000 ng/ ml of the toxin suppressed the LPS-induced IL-6 response. Four other 8-ketotrichothecenes, fusarenon X, nivalenol, 3-acetyl DON, and 15-acetyl DON, were also capable of upregulating or suppressing TNF- f , IL-6, and IL-8 production at concentrations similar to that of DON. In total, the results suggest that DON and other 8-ketotrichothecenes have the potential to both directly induce and superinduce proinflammatory cytokine and chemokine expression in human macrophages, even at toxin concentrations that are cytotoxic.