Physiology and pharmacology of the prostaglandin J2 family.
The prostaglandin (PG) J(2) family including PGJ(2), Delta(12)-PGJ(2), and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) are metabolites of PGD(2). They had been known as powerful inhibitors of cell proliferation and viral replication until 15d-PGJ(2) was found to be a natural ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). 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 PPAR gamma or not. We reported that the PGJ(2) family, particularly 15d-PGJ(2), inhibits cell proliferation by reducing the expression of G(1) 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-PGJ(2) 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 PGD(2) synthase, which converts PGH(2) to PGD(2), the precursor of the PGJ(2) family. Based on these results, we have hypothesized that the PGJ(2) family synthesized in vascular wall plays an important physiological role to protect vascular cells from atherogenic stimuli.
Miwa
Yoshikazu
Y
Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ymiwa@clipharm.med.kyushu-u.ac.jp
Taba
Yoji
Y
Miyagi
Megumi
M
Sasaguri
Toshiyuki
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2