The cyclopentenone prostaglandin 15-deoxy-Δ 12,14-prostaglandin J 2 attenuates the development of acute and chronic inflammation

Salvatore Cuzzocrea, Nicole S. Wayman, Emanuela Mazzon, Laura Dugo, Rosanna Di Paola, Ivana Serraino, Domenico Britti, Prabal K. Chatterjee, Achille P. Caputi, Christoph Thiemermann

Research output: Contribution to journalArticlepeer-review

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-γ 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-deoxy-Δ 12,14-PGJ 2 (15d-PGJ 2), which is a metabolite of prostaglandin D 2, functions as an endogenous ligand for PPAR-γ. 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 μg/kg i.p. in the pleurisy model or at 30 μg/kg i.p every 48 h in the arthritis model) exerts potent anti-nflammatory 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.

Original languageEnglish
Pages (from-to)997-1007
Number of pages11
JournalMolecular Pharmacology
Volume61
Issue number5
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Pharmacology

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