Wang Xing, Wang Yaling, Qiu Mei, Sun Lijun, Wang Xiaobo, Li Caihong, Xu Defeng, Gooneratne Ravi
College of Food Science and Technology , Guangdong Ocean University , Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety , Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution , Zhanjiang 524088 , China.
National Marine Products Quality Supervision & Inspection Center , Zhanjiang 524000 , China.
Toxicol Res (Camb). 2017 Jan 9;6(2):144-151. doi: 10.1039/c6tx00392c. eCollection 2017 Mar 1.
T-2 can be biotransformed in animal tissues to modified T-2s (mT-2s). Food contaminated with T-2 and/or mT-2s is a hazard to both animals and humans, including the immune system. In this study, were fed T-2 orally for 20 d, and hepatopancreas and muscle extracts, T-2, and T-2-glucuronide (T-2-GluA) were added to RAW264.7 and their effects on the JAK/STAT pathway were examined. STAT2 mRNA gene expression induced by hepatopancreas and muscle extracts was markedly higher compared with that of T-2 or T-2-GluA group. SCOSs, IL-6 and IL-1β mRNA gene expressions induced by hepatopancreas extract were greater than those induced by muscle extract. Muscle extract significantly activated STAT3 phosphorylation but inhibited STAT1 phosphorylation. Activation of the JAK/STAT pathway by hepatopancreas mT-2s was significantly higher than that by muscle extracts. Muscle and hepatopancreas extracts and T-2 also significantly induced IL-6 mRNA gene expression. With reference to phosphorylation levels, significant activation of JAK1 and STAT2 occurred with T-2 and JAK3 by muscle extract, JAK2 by hepatopancreas extract and STAT1 by T-2-GluA. This study showed that both T-2 and mT-2s are cytotoxic but the activation of the JAK/STAT pathway in RAW264.7 cells by T-2 was greater than that by mT-2s in hepatopancreas and muscle extracts from T-2-fed
T-2可在动物组织中生物转化为修饰型T-2（mT-2s）。被T-2和/或mT-2s污染的食物对动物和人类均有危害，包括对免疫系统。在本研究中，给动物口服T-2持续20天，将肝胰腺和肌肉提取物、T-2以及T-2-葡萄糖醛酸苷（T-2-GluA）添加到RAW264.7细胞中，并检测它们对JAK/STAT通路的影响。与T-2或T-2-GluA组相比，肝胰腺和肌肉提取物诱导的STAT2 mRNA基因表达明显更高。肝胰腺提取物诱导的SCOSs、IL-6和IL-1β mRNA基因表达大于肌肉提取物诱导的表达。肌肉提取物显著激活STAT3磷酸化，但抑制STAT1磷酸化。肝胰腺mT-2s对JAK/STAT通路的激活明显高于肌肉提取物。肌肉和肝胰腺提取物以及T-2也显著诱导IL-6 mRNA基因表达。就磷酸化水平而言，肌肉提取物使T-2和JAK3激活JAK1和STAT2，肝胰腺提取物激活JAK2，T-2-GluA激活STAT1。本研究表明，T-2和mT-2s均具有细胞毒性，但T-2对RAW264.7细胞中JAK/STAT通路的激活作用大于T-2喂养的肝胰腺和肌肉提取物中的mT-2s
