Studies on the Prostaglandin Synthesis Stimulated by Bacterial Lipopolysaccharide in Mouse Peritoneal Macrophages

Abstract

Production of inflammatory mediators by the host in response to bacterial lipopolysaccharide (LPS) is generally believed to be responsible for the pathogenesis of septic shock. One of the mediators associated with septic shock sequelae are arachidonic acid metabolites, including prostanoids and leukotrienes. Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in prostanoid synthesis of which there were very recently reported two different isotypes. Their activities and expressions are known to be regulated by different mechanisms. Also, differences in response to stimulators have been shown for the different cell types. Even in the macrophage populations, there have been reported diverse profiles of prostanoid synthesis. These discrepancies might be due to the differences in the underlying regulation mechanisms, but presently, little information is available regarding these. Thus, in order to get insights into these discrepancies, firstly, we compared the characteristics of LPS-induced prostanoid production in alveolar macrophages and mouse peritoneal macrophages and secondly, we examined whether variations of glucose concentration affect LPS-induced prostanoid synthesis and PGHS-2 activity in both cell types. Overall responses to LPS were qualitatively similar between both cell types, and LPS-induced TXB2 production was attenuated in high glucose media.