PGHS-2 Dependent Formation of 8-Epi PGF2α by Human Monocytes
Arachidonic acid is converted enzymatically into different prostaglandins (PG) by the activity of a key enzyme, PG-endoperoxide synthase (PGHS), which exhibits both bisoxygenase and peroxidase activity (1). Cell-specific isomerization or reduction of PGH2 by various synthases (isomerases) or reductases leads to the formation of different prostanoids (2). It has been demonstrated that mammalian cells contain two isoforms of PGHS referred to as PGHS-1 and PGHS-2, encoded by separated genes (3). PGHS-1 is constitutively expressed in most tissue including platelets, endothelial cells and monocytes. However, it is recognized that expresion of PGHS-1 may be regualted. For example, androgens upregulate PGHS-1 in seminiferous tubules (4), as do cytokines in bone marrow derived mast cells (5). PGHS-2 expression is readily induced by serum, growth factors, cytokines in wide variety of cell types (6,7). Conventionally, this has implied the predominant importance of this isoform in regulating the inflammatory response. Data consistent with this view of the roles of the two enzymes have been obtained from “knock out” mice (8–10). Thus, while the PGHS-1 knock out exhibits a normal phenotype (8), inflammatory responses were modified following disruption of the PGHS-2 gene (9).
KeywordsHuman Monocyte Bone Marrow Derive Mast Cell Fresh Peripheral Blood Mononuclear Cell Human Prostaglandin Prostanoid Level
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