Prostaglandin J2 series induces the gene expression of monocyte chemoattractant protein-1 during the maturation phase of cultured adipocytes

Abstract

Prostaglandin (PG) J2 series including Δ12-PGJ2 and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is the dehydration products of PGD2 that are biosynthesized through the cyclooxygenase (COX) pathway. These prostanoids are active ligands for peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis in adipocytes. Here we investigated whether PGJ2 derivatives can modulate the gene expression of monocyte chemoattractant protein-1 (MCP-1), a pro-inflammatory chemokine, during the maturation phase of adipocytes. Each of selective or nonselective inhibitors for COX isoforms suppressed significantly the accumulation of fats by interfering the induced expression of the PPARγ gene. Immunological assays of PGJ2 series revealed higher production of Δ12-PGJ2 than 15d-PGJ2 by cultured adipocytes, implicating the contribution of endogenous PGJ2 series to the stimulated adipogenesis. In addition, the increased transcription of MCP-1 was detectable at later maturation phase of adipogenesis, which was prevented by co-incubation with aspirin. Although 15d-PGJ2 was more potent than Δ12-PGJ2, both PGJ2 derivatives series had similar effects to rescue dose-dependently the expression of the MCP-1 gene attenuated by aspirin. These findings suggest that the expression of MCP-1 involved in adipocyte inflammation could be positively regulated by the PGJ2 series during adipogenesis in adipose tissue.