烟酰胺 N-甲基转移酶通过抑制促炎细胞因子表达来防止脱氧雪腐镰刀菌烯醇诱导的生长抑制。

Nicotinamide N-methyltransferase protects against deoxynivalenol-induced growth inhibition by suppressing pro-inflammatory cytokine expression.

机构信息

National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hanxi Key Lab. for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, China.

National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.

出版信息

Food Chem Toxicol. 2022 May;163:112969. doi: 10.1016/j.fct.2022.112969. Epub 2022 Mar 27.

DOI:10.1016/j.fct.2022.112969

PMID:35351591

Abstract

Deoxynivalenol (DON) is an inevitable contaminant in cereals for infants. Indeed, children's growth retardation caused by widespread DON pollution has become a global problem that cannot be ignored. Accumulating evidence has shown that DON stunts growth in children through pro-inflammatory cytokines. An exogenous increase of methylnicotinamide, a metabolite produced by nicotinamide N-methyltransferase (NNMT), has anti-inflammatory effects, but it is not clear whether NNMT has the same effect, and the role of NNMT in DON-induced inflammation and growth impairment remains indistinct. The present research reports that NNMT is an inflammatory self-protective factor in DON-exposed L02 cells. DON promoted the production of pro-inflammatory cytokines. Furthermore, DON increased NNMT to reduce pro-inflammatory cytokines, including interleukin (IL)-1β, IL-11 and IL-6, and thus increased IGF-1 and cell viability, alleviating the cell growth inhibition induced by DON. Interestingly, NNMT negatively regulated the expression of IL-1β through Sirtuin type 1 (SIRT1). Collectively, these findings provide new mechanistic insights into the toxicity of DON-induced growth retardation and inflammatory responses in children.

摘要

脱氧雪腐镰刀菌烯醇（DON）是婴幼儿谷物中不可避免的污染物。事实上，由于广泛的 DON 污染导致儿童生长迟缓，这已成为一个不容忽视的全球性问题。越来越多的证据表明，DON 通过促炎细胞因子阻碍儿童生长。烟酰胺 N-甲基转移酶（NNMT）产生的代谢物甲基烟酰胺的外源性增加具有抗炎作用，但尚不清楚 NNMT 是否具有相同的作用，NNMT 在 DON 诱导的炎症和生长损伤中的作用仍不清楚。本研究报告称，NNMT 是 DON 暴露的 L02 细胞中的一种炎症自我保护因子。DON 促进了促炎细胞因子的产生。此外，DON 增加了 NNMT 以减少促炎细胞因子，包括白细胞介素（IL）-1β、IL-11 和 IL-6，从而增加 IGF-1 和细胞活力，减轻 DON 诱导的细胞生长抑制。有趣的是，NNMT 通过 Sirtuin type 1（SIRT1）负调控 IL-1β 的表达。总之，这些发现为 DON 诱导的儿童生长迟缓和炎症反应的毒性提供了新的机制见解。