Zearalenone (ZEA)-induced intestinal inflammation is mediate

<p>&nbsp;</p> <p><b>&ldquo;上海酶聯文獻&rdquo;&nbsp;</b>Wentao Fan a, Yanan Lv a, Shuai Ren a, Manyu Shao a, Tongtong Shen a, Kehe Huang a, Jiyong Zhou a, b, Liping Yan a, b, **, Suquan Song a,&nbsp;</p> <p>aCollege of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China</p> <p>bJiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China</p> <p><strong>h i g h l i g h t s</strong></p> <p>ZEA increased NLRP3 inflammasome expression and cytokines release in cells. Elevated cytokines induced severe intestinal inflammation in ZEA-treated mice. ZEA induced colitis by activating ROS mediated NLRP3 inflammasome.</p> <p><strong>a r t i c l e i n f o</strong></p> <p>Article history:</p> <p>Received 4 August 2017</p> <p>Received in revised form</p> <p>21 September 2017</p> <p>Accepted 29 September 2017</p> <p>Available online 30 September 2017</p> <p>Handling Editor: A. Gies</p> <p><strong>Keywords:</strong></p> <p>Zearalenone</p> <p>NLRP3 inflammasome Pro-inflammatory cytokines Intestinal inflammation Reactive oxygen species</p> <p><strong>a b s t r a c t</strong></p> <p>To ascertain whether zearalenone (ZEA) could induce intestinal inflammation and investigate its possible mechanism, we investigated inflammatory cytokine release and the activation of the NLRP3 inflamma-some after ZEA treatment both in vitro or in vivo. First, intestinal porcine enterocyte cell line (IPEC-J2) cells and mouse peritoneal macrophages were treated with ZEA to detect NLRP3 inflammasome acti-vation, and the role of reactive oxygen species (ROS) in ZEA-induced inflammation was investigated. Then, Balb/c mice were fed a gavage of ZEA, and the disease activity indices (DAIs) and histological analysis were used to assess intestinal inflammation. Our study showed that the mRNA expression of NLRP3 inflammasome, pro-interleukin-1b (pro-IL-1b), and pro-interleukin-18 (pro-IL-18) was up-regulated 0.5- to 1-fold and that the release of IL-1b and IL-18 increased from 48 pg mL 1 to 55 pg mL 1 and 110 pg mL 1 to 145 pg mL 1, respectively. However, ROS inhibitor N-acetyl-L-cysteine (NAC) reduced IL-1b and IL-18 release to 45 pg mL 1 and 108 pg mL 1. Moreover, the same phenomenon was observed in intestinal tissues of ZEA-treated mice. In addition, clinical parameters of treated mice showed stools became loose and contained mucous. In addition, the presence of gross blood stool was found in the last 2 d. Histological analysis showed obvious inflammatory cell infiltration and tissue damage in the colon. These findings uncovered a possible mechanism of intestinal mucosal innate im-munity in response to mycotoxin ZEA that ZEA could activate the ROS-mediated NLRP3 inflammasome and, in turn, contribute to the caspase-1-dependent activation of the inflammatory cytokines IL-1b and IL-18.</p> <p><img src="/images/upload/Image/圖片3(4).png" width="362" height="518" alt="" /></p> <p><strong>References</strong></p> <p>Ascenzi, P., Bocedi, A., Marino, M., 2006. Structureefunction relationship of estro-gen receptor a and b: impact on human health. Mol. Aspect. Med. 27, 299e402.</p> <p>Bauer, C., Duewell, P., Mayer, C., Lehr, H.A., Fitzgerald, K.A., Dauer, M., Tschopp, J., Endres, S., Latz, E., Schnurr, M., 2010. Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. 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