The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) attenuates the development of acute and chronic inflammation.
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.
Cuzzocrea
Salvatore
S
Institute of Pharmacology, School of Medicine, University of Messina, Messina, Italy. salvator@unime.it
Wayman
Nicole S
NS
Mazzon
Emanuela
E
Dugo
Laura
L
Di Paola
Rosanna
R
Serraino
Ivana
I
Britti
Domenico
D
Chatterjee
Prabal K
PK
Caputi
Achille P
AP
Thiemermann
Christoph
C
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D002351:Carrageenan; D003517:Cyclopentanes / Q000737:chemistry; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000627:therapeutic use*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D003517:Cyclopentanes; D007155:Immunologic Factors; D002351:Carrageenan; C013905:cyclopentenone; D015230:Prostaglandin D2