Physiology and pharmacology of the prostaglandin J2 family

Abstract

The prostaglandin (PG) J2 family including PGJ2, Δ12-PGJ2, and 15-deoxy-Δ 12,14-PGJ2 (15d-PGJ2) are metabolites of PGD2. They had been known as powerful inhibitors of cell proliferation and viral replication until 15d-PGJ2 was found to be a natural ligand for peroxisome proliferator-activated receptor γ (PPARγ). Since then, several new pharmacological actions of the PGJ 2 family have been found, such as pro- and anti-apoptotic effects, cell differentiation-inducing effects, and inhibitory effects on inflammatory processes, whether they depend on PPARγ or not. We reported that the PGJ2 family, particularly 15d-PGJ2, inhibits cell proliferation by reducing the expression of G1 cyclins and inducing the expression of cyclin-dependent kinase inhibitor p21 and moreover, induces cell differentiation in vascular smooth muscle cells. In vascular endothelial cells, we found that 15d-PGJ2 inhibits apoptotic cell death at least in part by the induction of the inhibitor of apoptosis protein c-IAP1. More importantly, physiological levels of laminar fluid shear stress loaded on endothelial cells upregulate the expression of lipocalin-type PGD2 synthase, which converts PGH2 to PGD2, the precursor of the PGJ2 family. Based on these results, we have hypothesized that the PGJ2 family synthesized in vascular wall plays an important physiological role to protect vascular cells from atherogenic stimuli.