TY - JOUR
T1 - The cyclopentenone prostaglandin 15-deoxy-Δ 12,14-prostaglandin J 2 attenuates the development of acute and chronic inflammation
AU - Cuzzocrea, Salvatore
AU - Wayman, Nicole S.
AU - Mazzon, Emanuela
AU - Dugo, Laura
AU - Paola, Rosanna Di
AU - Serraino, Ivana
AU - Britti, Domenico
AU - Chatterjee, Prabal K.
AU - Caputi, Achille P.
AU - Thiemermann, Christoph
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1124/mol.61.5.997
DO - 10.1124/mol.61.5.997
M3 - Article
C2 - 11961117
AN - SCOPUS:18344370479
VL - 61
SP - 997
EP - 1007
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 5
ER -