Zearalenone (ZEA)-induced intestinal inflammation is mediate

“上海酶联文献” 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, 

aCollege of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China

bJiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China

h i g h l i g h t s

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.

a r t i c l e i n f o

Article history:

Received 4 August 2017

Received in revised form

21 September 2017

Accepted 29 September 2017

Available online 30 September 2017

Handling Editor: A. Gies

Keywords:

Zearalenone

NLRP3 inflammasome Pro-inflammatory cytokines Intestinal inflammation Reactive oxygen species

a b s t r a c t

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.

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