Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.
J Dairy Sci. 2010 Nov;93(11):5188-99. doi: 10.3168/jds.2010-3250.
The endotoxin-induced inflammatory response during coliform mastitis is difficult to control with the currently available therapeutics. Endothelial cells are among the first cell type to be engaged in the inflammatory response and can modulate the severity of inflammation by producing proinflammatory mediators upon endotoxin exposure. Ethyl pyruvate, an ethyl ester of pyruvic acid, can ameliorate endotoxin-induced inflammatory responses by inhibiting the production of proinflammatory mediators in several in vitro and in vivo endotoxemia models. The objective of this study was to determine the effect of ethyl pyruvate on the production of vascular proinflammatory mediators that are associated with the pathogenesis of coliform mastitis. The ability of ethyl pyruvate to reduce the expression of proinflammatory mediators was evaluated in cultured bovine mammary endothelial cells (BMEC) stimulated with endotoxin. Treatment of endotoxin-stimulated BMEC with ethyl pyruvate significantly reduced gene expression of IL-6, IL-8, and intercellular adhesion molecule 1 as well as expression of eicosanoid-producing enzymes, including cyclooxygenase 2 and 15-lipoxygenase 1. This is the first time that the effect of ethyl pyruvate was evaluated in an in vitro BMEC model of coliform mastitis. The ability of ethyl pyruvate to effectively inhibit gene and protein expression of potent vascular proinflammatory mediators in vitro warrants further investigations to assess in vivo efficacy. Ethyl pyruvate is safe for human consumption, and it may be an attractive candidate as a therapeutic in ameliorating the severe pathogenesis associated with coliform mastitis.
大肠杆菌性乳腺炎中内毒素诱导的炎症反应难以用现有疗法控制。内皮细胞是最早参与炎症反应的细胞类型之一，通过在接触内毒素时产生促炎介质，可以调节炎症的严重程度。丙酮酸乙酯是丙酮酸的乙酯，可以通过抑制几种体外和体内内毒素血症模型中促炎介质的产生来改善内毒素诱导的炎症反应。本研究的目的是确定丙酮酸乙酯对与大肠杆菌性乳腺炎发病机制相关的血管促炎介质产生的影响。通过用内毒素刺激培养的牛乳腺内皮细胞 (BMEC) 来评估丙酮酸乙酯降低促炎介质表达的能力。用丙酮酸乙酯处理内毒素刺激的 BMEC 可显著降低白细胞介素 6、白细胞介素 8 和细胞间黏附分子 1 的基因表达以及产生花生四烯酸的酶的表达，包括环加氧酶 2 和 15-脂加氧酶 1。这是丙酮酸乙酯在大肠杆菌性乳腺炎体外 BMEC 模型中首次进行评估。丙酮酸乙酯在体外有效抑制潜在血管促炎介质的基因和蛋白表达的能力需要进一步研究以评估其体内疗效。丙酮酸乙酯可安全用于人类消费，作为改善与大肠杆菌性乳腺炎相关的严重发病机制的治疗药物可能具有吸引力。
