title: Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.
abstract: One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.
authors.affiliation: Department of Internal Medicine, UCLA School of Medicine.
authors.forename: S G
authors.initials: SG
authors.lastname: Filler
authors.forename: B O
authors.initials: BO
authors.lastname: Ibe
authors.forename: A S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: M A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: J U
authors.initials: JU
authors.lastname: Raj
authors.forename: J E
authors.initials: JE
authors.lastname: Edwards
mesh_terms: D002176:Candida albicans / Q000472:pathogenicity*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D010740:Phospholipases / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000502:physiology
chemical_list: D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D010740:Phospholipases