Azcona-Olivera J I, Ouyang Y, Murtha J, Chu F S, Pestka J J
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824, USA.
Toxicol Appl Pharmacol. 1995 Jul;133(1):109-20. doi: 10.1006/taap.1995.1132.
The effects of oral exposure to 0, 5, and 25 mg/kg body wt vomitoxin (VT) on cytokine mRNA levels in spleen, Peyer's patches (PP), liver, kidney, and small intestine were evaluated in B6C3F1 mice at 2 and 4 hr postexposure using RT-PCR in conjunction with Southern hybridization analysis. The abundance of mRNAs for several cytokines was increased in VT-exposed mice with maximal effects occurring in the 25 mg/kg group at 2 hr. Specifically, IL-1 beta and IL-6 mRNA levels increased in spleen and PP following exposure to VT. TNF-alpha mRNA levels were markedly elevated in spleen and liver of VT-exposed mice. TGF-beta mRNA was increased in treatment kidneys and to a lesser extent in liver and small intestine. IFN-gamma mRNAs were elevated according to the rank order: spleen > PP > small intestine > liver > kidney, whereas IL-2 mRNAs were increased primarily in spleen and PP. VT had little effect on abundance of mRNAs for the TH2 cytokines, IL-4 and IL-5, or the housekeeping gene, hypoxanthine guanine ribosyl transferase. In order to relate cytokine mRNA abundance to toxin distribution, mice were administered 5 and 25 mg/kg VT body wt containing [3H]VT and tissue levels were monitored over time. Maximum VT molar equivalents for both doses were found at 30 min or 1 hr in all tissues with a rapid clearance following two-compartment kinetics over 24 hr. When effects of oral VT exposure on in vivo protein synthesis at 3 hr postexposure was measured using [14C]leucine uptake, it was found to be inhibited by > or = 20 and > or = 50% in tissues of mice receiving 5 and 25 mg/kg VT, respectively. While recovery was observed in tissues of the 5 mg/kg group at 6 hr, protein synthesis was still significantly inhibited (> or = 70%) at 9 hr for all tissues in the 25 mg/kg group. The results suggest that acute oral VT exposure resulted in the transient elevation of mRNAs for proinflammatory and TH1 cytokines. These effects occurred immediately after peak VT accumulation and concurrently with marked in vivo protein synthesis inhibition.
采用逆转录-聚合酶链反应（RT-PCR）结合Southern杂交分析方法，评估了B6C3F1小鼠经口暴露于0、5和25mg/kg体重呕吐毒素（VT）后2小时和4小时，脾脏、派伊尔结（PP）、肝脏、肾脏和小肠中细胞因子mRNA水平的变化。暴露于VT的小鼠中，几种细胞因子的mRNA丰度增加，最大效应出现在2小时时的25mg/kg组。具体而言，暴露于VT后，脾脏和PP中白细胞介素-1β（IL-1β）和IL-6 mRNA水平升高。暴露于VT的小鼠脾脏和肝脏中肿瘤坏死因子-α（TNF-α）mRNA水平显著升高。转化生长因子-β（TGF-β）mRNA在处理后的肾脏中增加，在肝脏和小肠中增加程度较小。干扰素-γ（IFN-γ）mRNA升高的顺序为：脾脏＞PP＞小肠＞肝脏＞肾脏，而IL-2 mRNA主要在脾脏和PP中增加。VT对TH2细胞因子IL-4和IL-5或管家基因次黄嘌呤鸟嘌呤核糖基转移酶的mRNA丰度影响较小。为了将细胞因子mRNA丰度与毒素分布相关联，给小鼠施用含有[3H]VT的5和25mg/kg VT体重剂量，并随时间监测组织水平。在所有组织中，两种剂量的最大VT摩尔当量在30分钟或1小时时出现，在24小时内遵循二室动力学快速清除。当使用[14C]亮氨酸摄取测量经口VT暴露对暴露后3小时体内蛋白质合成的影响时，发现接受5和25mg/kg VT的小鼠组织中蛋白质合成分别被抑制≥20%和≥50%。虽然在5mg/kg组的组织中6小时时观察到恢复，但在25mg/kg组的所有组织中9小时时蛋白质合成仍被显著抑制（≥70%）。结果表明，急性经口VT暴露导致促炎和TH1细胞因子的mRNA短暂升高。这些效应在VT积累峰值后立即出现，并与明显的体内蛋白质合成抑制同时发生。
