Modulation of Arachidonic Acid Metabolism in a Cultured Newborn Rat Keratinocytes Cell Line

Newborn rat keratinocytes, the NBR cell line, synthesized the cyclooxygenase metabolic products, prostaglandins E2 and F2« and the lipoxygenase metabolic product, hydroxyeicosatetraenoic acid. This metabolism was stimulated by incubation of the cells with the Ca+ + ionophore, A23187; melittin; bradykinin; recombinant human f-met epidermal growth factor; the tumor promoter, 12-O-tetradecanoyl-phorobol-13-acetate; and the synthetic analog of diacylglycerol, 1-oleoyl-2-acetyl glycerol. Production of the cyclooxygenase products was inhibited by the synthetic glucocorticoid, dexamethasone. The stimulation appeared to be modulated by deesterification of arachidonic acid from the cellular lipids, presumably by phospholipase A2. Increased intracellular levels of Ca+ + and phosphorylating activities that result from polyphosphoinositol turnover as well as phosphorylating activities independent of phosphatidylinositol turnover appear to be regulating phospholipase A2 hydrolysis of phospholipids