7β-hydroxy-epiandrosterone modulation of 15-deoxy-Δ^12,14-prostaglandin J₂, prostaglandin D₂ and prostaglandin E₂ production from human mononucle

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• 作者：Jillian Davidson ; Ernst Wulfert ; Dino Rotondo
• 关键词：Steroids ; 7β ; -Hydroxy-epiandrosterone ; 15d-PGJ₂ ; PGE₂ ; PGD₂ ; Human mononuclear cells ; Inflammation
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2008
• 出版时间：December 2008
• 年：2008
• 卷：112
• 期：4-5
• 页码：220-227
• 全文大小：619 K

文摘

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-Δ^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.