The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) attenuates the development of acute and chronic inflammation.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. The PPAR-gamma receptor subtype seems to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxyDelta(12,14)-PGJ(2) (15d-PGJ(2)), which is a metabolite of prostaglandin D(2), functions as an endogenous ligand for PPAR-gamma. We postulated that 15d-PGJ(2) would attenuate inflammation. In the present study, we have investigated the effects of 15d-PGJ(2) of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis, respectively) in animal models. We report for the first time, to our knowledge, that 15d-PGJ(2) (given at 10, 30, or 100 microg/kg i.p. in the pleurisy model or at 30 microg/kg i.p every 48 h in the arthritis model) exerts potent anti-inflammatory effects (e.g., inhibition of pleural exudate formation, mononuclear cell infiltration, delayed development of clinical indicators, and histological injury) in vivo. Furthermore, 15d-PGJ(2) reduced the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase and the expression of inducible nitric-oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated mice and in the joints from collagen-treated mice. Thus, 15d-PGJ(2) reduces the development of acute and chronic inflammation. Therefore, the cyclopentenone prostaglandin 15d-PGJ(2) may be useful in the therapy of acute and chronic inflammation.

• Authors: Salvatore Cuzzocrea, Nicole S Wayman, Emanuela Mazzon, Laura Dugo, Rosanna Di Paola, Ivana Serraino, Domenico Britti, Prabal K Chatterjee, Achille P Caputi, Christoph Thiemermann
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 61 Issue 5 Pg. 997-1007 (May 2002) ISSN: 0026-895X [Print] United States
• PMID: 11961117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxy-delta(12,14)-prostaglandin J2
• Cyclopentanes
• Immunologic Factors
• Carrageenan
• cyclopentenone
• Prostaglandin D2

Topics

• Animals
• Arthritis, Experimental (drug therapy, pathology)
• Carrageenan
• Cyclopentanes (chemistry)
• Disease Models, Animal
• Immunohistochemistry
• Immunologic Factors (therapeutic use)
• Inflammation (drug therapy, etiology)
• Male
• Mice
• Mice, Inbred BALB C
• Pleurisy (chemically induced, drug therapy, pathology)
• Prostaglandin D2 (analogs & derivatives, therapeutic use)