Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci

Group B streptococcal (GBS) infections are associated with high morbidity a nd mortality. The molecular pathways mediating the pathophysiological event s in GBS infection are not fully delineated. Cyclooxygenases (COX) are the enzymes that convert arachidonate to active eicosanoids. To identify the ef fects of GBS on eicosanoid metabolism and regulatory mechanisms, we exposed human monocytes to GBS and found that they secreted prostaglandin E-2, pro stacyclin, and thromboxane A(2), Exposure to GBS caused monocytes to expres s COX-2 mRNA and protein in both a time- and concentration-dependent manner that correlated with eicosanoid production. COX-1 protein was unchanged. A ddition of the anti-inflammatory cytokines interleukin (IL)-4 or IL-10 mark edly attenuated GBS-induced COX-2 protein accumulation after GBS exposure, as did inhibition of p38 MAPK. Our experiments are the first to show that e xposure of monocytes to a gram-positive bacterium (GBS) results in inductio n of functional COX-2, suggesting that eicosanoids may play important roles in the pathogenesis of GBS infections.