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

Jillian Davidson, Ernst Wulfert, Dino Rotondo

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.
LanguageEnglish
Pages220-227
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume112
Issue number4-5
DOIs
Publication statusPublished - Dec 2008

Fingerprint

Prostaglandin D2
Dinoprostone
Modulation
Prostaglandins
Tumor Necrosis Factor-alpha
Arachidonic Acid
Biosynthesis
7-hydroxyandrosterone
hydroxide ion
9-deoxy-delta-9-prostaglandin D2
Metabolites
Immunoenzyme Techniques
Interleukin-10
Brain
Anti-Inflammatory Agents
Cytokines

Keywords

  • steroids
  • 7 beta-Hydroxy-epiandrosterone
  • 15d-PGJ(2)
  • PGE(2)
  • PGD(2)
  • human mononuclear cells
  • inflammation

Cite this

@article{2749b058e9c24ec4a29f45e8ca3afe84,
title = "7β-hydroxy-epiandrosterone modulation of 15-deoxy-Δ12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 production from human mononuclear cells",
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.",
keywords = "steroids, 7 beta-Hydroxy-epiandrosterone, 15d-PGJ(2), PGE(2), PGD(2), human mononuclear cells, inflammation",
author = "Jillian Davidson and Ernst Wulfert and Dino Rotondo",
year = "2008",
month = "12",
doi = "10.1016/j.jsbmb.2008.10.007",
language = "English",
volume = "112",
pages = "220--227",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
number = "4-5",

}

TY - JOUR

T1 - 7β-hydroxy-epiandrosterone modulation of 15-deoxy-Δ12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 production from human mononuclear cells

AU - Davidson, Jillian

AU - Wulfert, Ernst

AU - Rotondo, Dino

PY - 2008/12

Y1 - 2008/12

N2 - 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.

AB - 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.

KW - steroids

KW - 7 beta-Hydroxy-epiandrosterone

KW - 15d-PGJ(2)

KW - PGE(2)

KW - PGD(2)

KW - human mononuclear cells

KW - inflammation

U2 - 10.1016/j.jsbmb.2008.10.007

DO - 10.1016/j.jsbmb.2008.10.007

M3 - Article

VL - 112

SP - 220

EP - 227

JO - Journal of Steroid Biochemistry and Molecular Biology

T2 - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 4-5

ER -