+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

7beta-hydroxy-epiandrosterone modulation of 15-deoxy-delta12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 production from human mononuclear cells



7beta-hydroxy-epiandrosterone modulation of 15-deoxy-delta12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 production from human mononuclear cells



Journal of Steroid Biochemistry and Molecular Biology 112(4-5): 220-227



7beta-hydroxy-epiandrosterone (7beta-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-Delta12,14-prostaglandin J2 (15d-PGJ2) are also cytoprotective. It is possible that these prostaglandins derived from circulating mononuclear cells may mediate the actions of 7beta-OH-EPIA. The aim of this study, therefore, was to ascertain the effect of 7beta-OH-EPIA (in the absence or presence of tumour necrosis factor-alpha (TNF-alpha)), a pro-inflammatory stimulus, on the biosynthesis of PGD2, PGE2 and 15d-PGJ2 from human mononuclear cells. Prostaglandins were measured by enzyme immunoassay (EIA). 7beta-OH-EPIA alone induced a concentration-dependant increase in the production of PGD2. TNF-alpha increased PGD2 levels which were enhanced by 7beta-OH-EPIA. 7beta-OH-EPIA increased 15d-PGJ2 levels both in the absence and presence of TNF-alpha. 7beta-OH-EPIA alone had no effect on PGE2 biosynthesis but suppressed TNF-alpha-induced PGE2 circa 50%. 7beta-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. 7beta-OH-EPIA did not affect levels of the anti-inflammatory cytokine IL-10 indicating that this is an unlikely mechanism by which 7beta-OH-EPIA induces its actions but more likely exerts its effects via the production of cytoprotective prostaglandins.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051052463

Download citation: RISBibTeXText

PMID: 18996481

DOI: 10.1016/j.jsbmb.2008.10.007


Related references

Augmentation of lipogenesis by 15-deoxy-Delta12,14-prostaglandin J2 in hamster sebaceous glands: identification of cytochrome P-450-mediated 15-deoxy-Delta12,14-prostaglandin J2 production. Journal of Investigative Dermatology 125(5): 865-872, 2005

Stress protein activation by the cyclopentenone prostaglandin 15-deoxy-delta12,14-prostaglandin J2 in human mesangial cells. Kidney International 65(3): 798-810, 2004

Prostaglandins and congeners part 9 the synthesis of 15 deoxy 16 hydroxy prostaglandin 15 deoxy 17 hydroxy prostaglandin or 15 deoxy 20 hydroxy prostaglandin and 15 deoxy 15 hydroxymethyl prostaglandin e 2. Prostaglandins: 289-296, 1975

Targeting of epidermal growth factor receptor by cyclopentenone prostaglandin 15-Deoxy-Delta12,14-prostaglandin J2 in human oral squamous carcinoma cells. Cancer Letters 211(1): 97, 2004

7beta-Hydroxy-epiandrosterone-mediated regulation of the prostaglandin synthesis pathway in human peripheral blood monocytes. Steroids 73(11): 1148-1159, 2008

15-Deoxy-delta12,14-prostaglandin-J(2) up-regulates cyclooxygenase-2 but inhibits prostaglandin-E(2) production through a thiol antioxidant-sensitive mechanism. Pharmacological Research 57(5): 344-350, 2008

Prostaglandin J2 and 15-deoxy-delta12,14-prostaglandin J2 induce proliferation of cyclooxygenase-depleted colorectal cancer cells. Cancer Research 59(11): 2739-2746, 1999

Upregulation of interleukin-8 expression by prostaglandin D2 metabolite 15-deoxy-delta12, 14 prostaglandin J2 (15d-PGJ2) in human THP-1 macrophages. Atherosclerosis 160(1): 11-20, 2002

Differential effects of serum constituents on apoptosis induced by the cyclopentenone prostaglandin 15-deoxy-delta12,14-prostaglandin J2 in WISH epithelial cells. Prostaglandins Leukotrienes and Essential Fatty Acids 71(3): 191-197, 2004

Involvement of c-jun N-terminal kinase activation in 15-deoxy-delta12,14-prostaglandin J2-and prostaglandin A1-induced apoptosis in AGS gastric epithelial cells. Molecular Carcinogenesis 37(1): 16-24, 2003

Inhibition of proinflammatory cytokines by 15-deoxy-DELTA12,14-prostaglandin J2 is independent of PPARgamma in human peripheral blood mononuclear cells. Inflammation Research 52(Suppl. 2): S 152, 2003

Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma and levels of prostaglandin E2 and 15-deoxy-delta12,14-prostaglandin J2 in human breast cancer and metastasis. International Journal of Cancer 103(1): 84-90, 2003

Anti-inflammatory effects and changes in prostaglandin patterns induced by 7beta-hydroxy-epiandrosterone in rats with colitis. Journal of Steroid Biochemistry and Molecular Biology 110(3-5): 255-262, 2008

Inhibition of trail gene expression by cyclopentenonic prostaglandin 15-deoxy-delta12,14-prostaglandin J2 in T lymphocytes. Molecular Pharmacology 72(5): 1246-1257, 2007

S. aureus-dependent microglial activation is selectively attenuated by the cyclopentenone prostaglandin 15-deoxy-Delta12,14- prostaglandin J2 (15d-PGJ2). Journal of Neurochemistry 90(5): 1163-1172, 2004