Ethyl pyruvate protects against Salmonella intestinal infection in mice through down-regulation of pro-inflammatory factors and inhibition of TLR4/MAPK pathway

被引:25
|
作者
Dong, Na [1 ]
Xu, Xinyao [1 ]
Xue, Chenyu [1 ]
Wang, Chensi [1 ]
Li, Xinran [1 ]
Shan, Anshan [1 ]
Xu, Li [1 ]
Li, Deshan [2 ]
机构
[1] Northeast Agr Univ, Inst Anim Nutr, Lab Mol Nutr & Immun, Harbin, Heilongjiang, Peoples R China
[2] Northeast Agr Univ, Coll Life Sci, Biopharmaceut Lab, Harbin, Heilongjiang, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
Ethyl pyruvate; Salmonella typhimurium; Intestinal immunity; TLR4; MAPK; NF-KAPPA-B; ANTIINFLAMMATORY ACTIVITY; EPITHELIAL BARRIER; SIGNALING PATHWAYS; PREVENTS; CELLS; ACTIVATION; INJURY; TIGHT; RESISTANCE;
D O I
10.1016/j.intimp.2019.03.019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Salmonella typhimurium is one of the main causes of intestinal diseases, affecting the health of humans and livestock. Ethyl pyruvate (EP), which is ordinarily an edible spice, has been indicated to exert anti-inflammatory effects and preserve intestinal barrier function. In this study, intestinal immune function and signaling pathways activated by EP were investigated in vivo in S. typhimurium-challenged BALB/c mice and in vitro in RAW264.7 cells. EP improved body weight loss and the organ index of the liver and spleen (p < 0.05). Serum IgA and IgM levels were significantly increased in EP-treated mice (p < 0.05). According to histopathological and immunohistochemical staining, EP significantly increased the villus height, reduced edema in the jejunum and increased the levels of claudin-1, occludin-1 and ZO-1 proteins compared to the Salmonella-treated group (p < 0.05). In addition, EP decreased the levels of the IL-6, IL-1 beta and TNF-alpha mRNA levels in jejunum, liver, spleen and RAW264.7 cells (p < 0.05). EP decreased the levels of TLR4, phosphorylated p38MAPK and ERK1/2 in mice infected with S. typhimurium (p < 0.05). In conclusion, EP effectively protected BALB/c mice from an intestinal S. typhimurium infection by improving the activity of the humoral immune system, reducing intestinal barrier damage, and inhibiting proinflammatory cytokine production in the jejunum by modulating the TLR4/MAPK signaling pathway. Based on these findings, EP has the potential to inhibit inflammation or to serve as an immune-enhancing adjuvant.
引用
收藏
页码:155 / 163
页数:9
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