Introduction: With the ingestion of mycotoxins-contaminated food or feed, the intestine will be exposed to high concentrations of toxin which will certainly influence the intestinal tract health. Previous study has shown that zearalenone (ZEA), a most popular poisonous mycotoxins, could lead to ROS accumulation in intestinal cell, which may induce the intestinal inflammation.
Methods: In order to ascertain if ZEA could induce inflammation in intestine and its possible mechanism, in our research, we treated the IPEC-J2 cells with different concentration of ZEA. And the ROS inhibitor N-acetyl-L-cysteine (NAC) were used to investigate the role of ROS in ZEA-induced intestinal inflammation. Simultaneously the BALB/c mice were fed with gavage of ZEA. Then the total RNA and protein of cells and intestine tissue were extracted, and the inflammasome activation and the release of inflammatory cytokines were carefully evaluated. Additionally the disease activity index (DAI) and histological analysis were applied to assess intestinal inflammation in mice.
Results: Our study showed the expression of NLRP3, ASC, caspase-1, pro-IL-1β, and pro-IL-18 were upregulated in cells with incubation of ZEA, and the release of IL-1β and IL-18 was largely promoted, which meant the initial inflammasome priming. However, these cytokines enhancement could be alleviated by NAC. In addition, the same phenomenon were observed in intestinal tissues of ZEA treated mice. And histological analysis showed obvious inflammatory cells infiltration and tissue damage. But the clinical parameters, including loss of body weight, the presence of occult or gross blood per rectum and stool consistency, were not as serious as dextran sulfate sodium (DSS) induced colitis.
Conclusion: These findings uncovered the possible mechanism of intestinal mucosal innate immunity in response to mycotoxins ZEA. That is ZEA could activate ROS mediated NLRP3 inflammasome, which then contribute to the casapase-1 dependent activation of inflammatory cytokines IL-1β and IL-18.