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真菌毒素玉米赤霉烯酮和脱氧雪腐镰刀菌烯醇通过抑制 TLR2/NFκB 信号通路降低乙型肝炎病毒感染后肝细胞固有免疫应答。

Mycotoxins Zearalenone and Deoxynivalenol Reduce Hepatocyte Innate Immune Response after the Infection by Inhibiting the TLR2/NFκB Signaling Pathway.

机构信息

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.

出版信息

Int J Mol Sci. 2023 Jun 2;24(11):9664. doi: 10.3390/ijms24119664.

Abstract

Zearalenone (ZEA) and deoxynivalenol (DON) are two common mycotoxins produced by the genus and have potential immunotoxic effects that may lead to a weak immune response against bacterial infections. (), a food-borne pathogenic microorganism ubiquitous in the environment, actively multiplies in the liver, where hepatocytes are capable of resistance through mediated innate immune responses. At present, it is not clear if ZEA and DON affect hepatocyte immune responses to infection or the mechanisms involved. Therefore, in this study, in vivo and in vitro models were used to investigate the effects of ZEA and DON on the innate immune responses of hepatocytes and related molecules after infection. In vivo studies revealed that ZEA and DON inhibited the toll-like receptors 2 (TLR2)/nuclear factor kappa-B (NFκB) pathway in the liver tissue of -infected mice, downregulating the expression levels of Nitric oxide (NO), in the liver and repressing the immune response. In addition, ZEA and DON inhibited Lipoteichoic acid (LTA)-induced expression of TLR2 and myeloid differentiation factor 88 (MyD88) in Buffalo Rat Liver (BRL 3A) cells in vitro, downregulating the TLR2/NFκB signaling pathway and resulting in the decreased expression levels of NO, causing immunosuppressive effects. In summary, ZEA and DON can negatively regulate NO levels through TLR2/NFκB, inhibiting the innate immune responses of the liver, and aggravate infections in mouse livers.

摘要

玉米赤霉烯酮(ZEA)和脱氧雪腐镰刀菌烯醇(DON)是两种常见的镰刀菌属真菌产生的霉菌毒素,具有潜在的免疫毒性作用,可能导致对细菌感染的免疫应答减弱。 (),一种食源性致病菌,在环境中无处不在,在肝脏中积极繁殖,肝细胞通过介导固有免疫反应具有抵抗能力。目前,尚不清楚 ZEA 和 DON 是否会影响肝细胞对 感染的免疫反应或涉及的机制。因此,在这项研究中,使用体内和体外模型来研究 ZEA 和 DON 对 感染后肝细胞固有免疫反应和相关分子的影响。体内研究表明,ZEA 和 DON 抑制了感染小鼠肝脏组织中的 toll 样受体 2(TLR2)/核因子 kappa-B(NFκB)途径,下调了肝脏中一氧化氮(NO)的表达水平,并抑制了免疫反应。此外,ZEA 和 DON 抑制了脂磷壁酸(LTA)诱导的 Buffalo Rat Liver(BRL 3A)细胞中 TLR2 和髓样分化因子 88(MyD88)的表达,下调了 TLR2/NFκB 信号通路,导致 NO 的表达水平降低,产生免疫抑制作用。综上所述,ZEA 和 DON 可以通过 TLR2/NFκB 负调控 NO 水平,抑制肝脏的固有免疫反应,加重小鼠肝脏中的 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8d2/10253956/a030d2cf7ef9/ijms-24-09664-g001.jpg

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