Wang, XWang, YalingWang, YSun, LGooneratne, SR2018-05-222017-05-302017-06-142017-05-290021-856128556663 (pubmed)https://hdl.handle.net/10182/9429T-2 toxin (T-2), one of the most toxic trichothecene A-type mycotoxins, is biotransformed in animal tissues to modified T-2s (mT-2s) including T-2 glucuronide (T-2-GlcA). In this study, the optimal conditions for T-2-GlcA synthesis were established, and the JAK/STAT pathway in RAW264.7 cells was used to study the toxicity of T-2-GlcA. Because many mT-2 standards are not readily available, optimal conditions for T-2-GlcA synthesis in vitro were established by incubating T-2 with rat liver microsomes, UDPGA, and 0.2% Triton X-100 for 90 min. qRT-PCR and Western blot results showed 21- and 760-fold increases in IL-6 mRNA expression induced by T-2-GlcA and T-2, respectively. Similar differences were observed in JAK3, SOCS2/3, and CIS mRNA expression. T-2-GlcA induced a dose-responsive decrease in STAT1 mRNA expression, whereas the result with T-2 was the opposite. Moreover, the phosphorylation of STAT3 induced by T-2-GlcA was higher than that by T- 2, whereas the phosphorylation of STAT1 was to the contrary. Overall, the results show that T-2-GlcA was somewhat toxic, but activation of the JAK/STAT pathway in RAW264.7 was higher by T-2.pp.4811-4818Print-Electronicen© 2017 American Chemical SocietyT-2-glucuronideT-2 toxinliver microsomesUDPGTimmune-toxicityMicrosomes, LiverMacrophagesAnimalsMiceRatsT-2 ToxinSignal TransductionPhosphorylationSTAT1 Transcription FactorSTAT3 Transcription FactorJanus Kinase 3RAW 264.7 CellsJournal Article10.1021/acs.jafc.7b01250ANZSRC::0601 Biochemistry and Cell BiologyANZSRC::111506 Toxicology (incl. Clinical Toxicology)1520-5118ANZSRC::30 Agricultural, veterinary and food sciencesANZSRC::34 Chemical sciencesANZSRC::40 Engineering