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Vol. 61, Issue 5, 997-1007, May 2002
12,14-Prostaglandin J2
Attenuates the Development of Acute and Chronic Inflammation
Institute of Pharmacology (S.C., L.D., R.D.P., I.S., A.P.C.),
Department of Biomorphology (E.M.), University of Messina, Messina,
Italy; Department of Experimental Medicine and Nephrology, the William
Harvey Research Institute, St. Bartholomew's and The Royal London
School of Medicine and Dentistry, London, United Kingdom (N.S.W.,
P.K.C., C.T.); and Department of Veterinary and Agricultural Science,
University of Teramo, Teramo, Italy (D.B.)
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-
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
12,14-PGJ2
(15d-PGJ2), which is a metabolite of
prostaglandin D2, functions as an endogenous ligand for
PPAR-. 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.
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