title: The 15-deoxy-δ12,14-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 PPARγ, 15-deoxy-δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) possesses immunomodulatory properties. The aim of this study was to elucidate whether 15d-PGJ(2) 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-PGJ(2). ARPE19 cells treated with varying concentrations of 15d-PGJ(2) and a PAF antagonist (CV3988) were used in this study. The activity of PAF-acetylhydrolase (PAF-AH) was assayed by treatment with 15d-PGJ(2) and CV3988 in the presence of LPS. 15d-PGJ(2) 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-PGJ(2) were not abrogated by the PPARγ antagonist, indicating that the actions were PPARγ-independent. Furthermore, 15d-PGJ(2) and CV3988 enhanced the PAF-AH activity. Additionally, 15d-PGJ(2) inhibited the phosphorylation of the extracellular signal-regulated kinase (ERK) and the activation of nuclear transcription factor-κB (NF-κB). These results demonstrated that 15d-PGJ(2) reduced LPS-stimulated inflammatory responses in ARPE19 cells by enhancing the PAH-AH activity. These results suggest that 15d-PGJ(2) may have potent anti-inflammatory activity against ocular inflammation.
authors: Department of Biomedical Engineering, Pukyong National University, Busan, Republic of Korea.
authors: Won-Kyo
authors: WK
authors: Jung
authors: Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine, Yang-san, Republic of Korea.
authors: Chang-Min
authors: CM
authors: Lee
authors: POSTECH Ocean Science and Technology Institute, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors: Dae-Sung
authors: DS
authors: Lee
authors: Department of Microbiology, College of Medicine Inje University, Busan, Republic of Korea.
authors: Giyoun
authors: G
authors: Na
authors: Department of Microbiology, College of Medicine Inje University, Busan, Republic of Korea.
authors: Da-Young
authors: DY
authors: Lee
authors: Department of Microbiology, College of Medicine Inje University, Busan, Republic of Korea.
authors: Inhak
authors: I
authors: Choi
authors: Department of Microbiology, College of Medicine Inje University, Busan, Republic of Korea.
authors: Sae-Gwang
authors: SG
authors: Park
authors: Department of Microbiology, College of Medicine Inje University, Busan, Republic of Korea.
authors: Su-Kil
authors: SK
authors: Seo
authors: Department of Ophthalmology, Busan Paik Hospital, College of Medicine Inje University, Busan, Republic of Korea.
authors: Jae-Wook
authors: JW
authors: Yang
authors: Department of Internal Medicine, Busan Paik Hospital, College of Medicine Inje University, Busan, Republic of Korea.
authors: Jung Sik
authors: JS
authors: Choi
authors: Department of Internal Medicine, Busan Paik Hospital, College of Medicine Inje University, Busan, Republic of Korea.
authors: Young-Min
authors: YM
authors: Lee
authors: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Republic of Korea.
authors: Won Sun
authors: WS
authors: Park
authors: Department of Microbiology, College of Medicine Inje University, Busan, Republic of Korea.
authors: Il-Whan
authors: IW
authors: Choi
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000166:cytology; D000093242:Interleukin-6 Inhibitors
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D048049:Extracellular Signal-Regulated MAP Kinases; D018799:Intercellular Adhesion Molecule-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D015230:Prostaglandin D2; D000093242:Interleukin-6 Inhibitors; C097240:15-deoxy-delta(12,14)-prostaglandin J2; C111835:CCL2 protein, human