Ethyl pyruvate diminishes the endotoxin-induced inflammatory response of bovine mammary endothelial cells

Abstract

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.