The 15-deoxy-d12,14-prostaglandin J2 inhibits LPS-stimulated inflammation via enhancement of the platelet-activating factor acetylhydrolase activity in human retinal pigment epithelial cells

Abstract

A well-recognized natural ligand of PPAR?, 15-deoxy-d12,14-prostaglandin J2 (15d-PGJ2) possesses immunomodulatory properties. The aim of this study was to elucidate whether 15d-PGJ2 was able to attenuate lipopolysaccharide (LPS)-induced inflammatory responses in human retinal pigment epithelial (RPE) cells, which are involved in ocular immune responses. In addition, we examined whether the platelet activating factor (PAF) is associated with the anti-inflammatory activity of 15d-PGJ2. ARPE19 cells treated with varying concentrations of 15d-PGJ2 and a PAF antagonist (CV3988) were used in this study. The activity of PAF-acetylhydrolase (PAF-AH) was assayed by treatment with 15d-PGJ2 and CV3988 in the presence of LPS. 15d-PGJ2 and CV3988 inhibited the LPS-induced mRNA expression and protein production of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) in ARPE19 cells. These effects resulting from 15d-PGJ2 were not abrogated by the PPAR? antagonist, indicating that the actions were PPAR?-independent. Furthermore, 15d-PGJ2 and CV3988 enhanced the PAF-AH activity. Additionally, 15d-PGJ2 inhibited the phosphorylation of the extracellular signal-regulated kinase (ERK) and the activation of nuclear transcription factor-?B (NF-?B). These results demonstrated that 15d-PGJ2 reduced LPS-stimulated inflammatory responses in ARPE19 cells by enhancing the PAH-AH activity. These results suggest that 15d-PGJ2 may have potent anti-inflammatory activity against ocular inflammation.