Ethyl pyruvate protects against Salmonella intestinal infection in mice through down-regulation of pro-inflammatory factors and inhibition of TLR4/MAPK pathway
Ethyl pyruvate protects against Salmonella intestinal infection in mice through down-regulation of pro-inflammatory factors and inhibition of TLR4/MAPK pathway
复制标题
丙酮酸乙酯通过下调促炎因子和抑制 TLR4/MAPK 通路来预防小鼠沙门氏菌肠道感染
DOI：
10.1016/j.intimp.2019.03.019
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发表时间：
2019-06-01
影响因子：
5.6
通讯作者：
Li, Deshan
中科院分区：
文献类型：
--
作者：
Dong, Na;Xu, Xinyao;Li, Deshan
鼠伤寒沙门氏菌是引起肠道疾病的主要原因之一，影响着人类和牲畜的健康。丙酮酸乙酯（EP）通常是一种食用香料，具有抗炎作用和保持肠道屏障功能。本研究在鼠伤寒沙门氏菌攻击BALB/c小鼠体内和体外RAW264.7细胞中研究了EP激活的肠道免疫功能和信号通路。EP提高了体重减轻率和肝脏、脾脏脏器指数（p < 0.05）。ep处理小鼠血清IgA和IgM水平显著升高（p < 0.05）。组织病理学和免疫组化染色结果显示，与沙门氏菌处理组相比，EP显著增加了大鼠空肠绒毛高度，减少了空肠水肿，提高了claudin-1、occludin-1和ZO-1蛋白水平（p < 0.05）。EP降低了大鼠空肠、肝脏、脾脏和RAW264.7细胞IL-6、IL-1 β和tnf - α mRNA水平（p < 0.05）。EP降低鼠伤寒沙门氏菌感染小鼠的TLR4、磷酸化p38MAPK和ERK1/2水平（p < 0.05）。综上所述，EP通过调节TLR4/MAPK信号通路，提高体液免疫系统活性，减轻肠道屏障损伤，抑制空肠促炎细胞因子的产生，从而有效保护BALB/c小鼠免受肠道鼠伤寒沙门氏菌感染。基于这些发现，EP具有抑制炎症或作为免疫增强佐剂的潜力。
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.