PMID: 11310850Apr 20, 2001Paper

Differential effects of 15-deoxy-delta(12,14)-prostaglandin J2 and a peroxisome proliferator-activated receptor gamma agonist on macrophage activation

Journal of Leukocyte Biology
K GuytonJ Cook

Abstract

Prostaglandin J2 metabolite 15-deoxy-delta(12,14)-prostaglandin J2 (15-PGJ2) appears to possess anti-inflammatory properties. Unlike other prostaglandins, it has no known plasma membrane receptor. Its effects have been thought to occur through activation of the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma), but 15-PGJ2 may exhibit effects independent of PPARgamma. We hypothesized that 15-PGJ2 modulates macrophage (Mphi) mediator production by acting on cell signaling proteins upstream of PPARgamma. The effects of 15-PGJ2 on bacterial endotoxin LPS-induced rat peritoneal Mphi mediator production were compared with those of a specific PPARgamma agonist, BRL 49653 (BRL), and to the eicosanoids prostaglandin D2 (PGD2) and cicaprost (CICA, a prostacyclin analogue). 15-PGJ2 inhibited LPS-induced production of NO, TNF-alpha, and thromboxane B2 (TxB2). Equimolar concentrations of PGD2 and CICA significantly inhibited LPS-stimulated TNF-alpha but not NO, and CICA increased TxB2 production. BRL inhibited LPS-induced NO, but augmented LPS-induced TNF-alpha and TxB2. 15-PGJ2 also inhibited degradation of LPS-induced IkappaB alpha and phosphoactivation of ERK 1/2, but BRL had no significant effect on either protein. T...Continue Reading

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