7β-hydroxy-epiandrosterone modulation of 15-deoxy-Δ12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 production from human mononuclear cells

Davidson, Jillian and Wulfert, Ernst and Rotondo, Dino (2008) 7β-hydroxy-epiandrosterone modulation of 15-deoxy-Δ12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 production from human mononuclear cells. Journal of Steroid Biochemistry and Molecular Biology, 112 (4-5). pp. 220-227. ISSN 0960-0760

Abstract

7β-hydroxy-epiandrosterone (7β-OH-EPIA) has been shown to be cytoprotective in various organs including the brain. It has also been shown that prostaglandin D2 (PGD2) and its spontaneous metabolite 15-deoxy--12,14-prostaglandin J2 (15d-PGJ2) are also cytoprotective. It is possible that these prostaglandins derived from circulating mononuclear cells may mediate the actions of 7β-OH-EPIA. The aim of this study, therefore, was to ascertain the effect of 7β-OH-EPIA (in the absence or presence of tumour necrosis factor-α (TNF-α)), a pro-inflammatory stimulus, on the biosynthesis of PGD2, PGE2 and 15d-PGJ2 from human mononuclear cells. Prostaglandins were measured by enzyme immunoassay (EIA). 7β-OH-EPIA alone induced a concentration-dependant increase in the production of PGD2. TNF-α increased PGD2 levels which were enhanced by 7β-OH-EPIA. 7β-OH-EPIA increased 15d-PGJ2 levels both in the absence and presence of TNF-α. 7β-OH-EPIA alone had no effect on PGE2 biosynthesis but suppressed TNF-α-induced PGE2 circa 50%. 7β-OH-EPIA also increased the level of free arachidonic acid and radiolabelled prostaglandins in cells pre-incubated with radiolabelled arachidonic acid, indicating that the increase may occur via the enhanced release of substrate arachidonic acid. 7β-OH-EPIA did not affect levels of the anti-inflammatory cytokine IL-10 indicating that this is an unlikely mechanism by which 7β-OH-EPIA induces its actions but more likely exerts its effects via the production of cytoprotective prostaglandins.

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