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-deoxyΔ12,14-PGJ2(15d-PGJ2), which is a metabolite of prostaglandin D2, functions as an endogenous ligand for PPAR-γ. We postulated that 15d-PGJ2 would attenuate inflammation. In the present study, we have investigated the effects of 15d-PGJ2 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-PGJ2 (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-inflammatory effects (e.g., inhibition of pleural exudate formation, mononuclear cell infiltration, delayed development of clinical indicators, and histological injury) in vivo. Furthermore, 15d-PGJ2 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-PGJ2 reduces the development of acute and chronic inflammation. Therefore, the cyclopentenone prostaglandin 15d-PGJ2 may be useful in the therapy of acute and chronic inflammation.
- The American Society for Pharmacology and Experimental Therapeutics
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