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

Jung,Won-Kyo; Lee,Chang-Min; Lee,Dae-Sung; Na,Giyoun; Lee,Da-Young; Choi,Inhak; Park,Sae-Gwang; Seo,Su-Kil; Yang,Jae-Wook; Choi,Jung  Sik; Lee,Young-Min; Park,Won Sun; Choi,Il-Whan

doi:10.3892/ijmm.2013.1588

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

Authors:
- Won-Kyo Jung
- Chang-Min Lee
- Dae-Sung Lee
- Giyoun Na
- Da-Young Lee
- Inhak Choi
- Sae-Gwang Park
- Su-Kil Seo
- Jae-Wook Yang
- Jung Sik Choi
- Young-Min Lee
- Won Sun Park
- Il-Whan Choi
View Affiliations

Affiliations: Department of Biomedical Engineering, Pukyong National University, Busan, Republic of Korea, Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine, Yang-san, Republic of Korea, POSTECH Ocean Science and Technology Institute, Pohang University of Science and Technology, Pohang, Republic of Korea, Department of Microbiology, College of Medicine Inje University, Busan, Republic of Korea, Department of Ophthalmology, Busan Paik Hospital, College of Medicine Inje University, Busan, Republic of Korea, Department of Internal Medicine, Busan Paik Hospital, College of Medicine Inje University, Busan, Republic of Korea, Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
Published online on: December 13, 2013 https://doi.org/10.3892/ijmm.2013.1588
Pages: 449-456

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

A well-recognized natural ligand of PPARγ, 15-deoxy-δ12,14-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 PPARγ antagonist, indicating that the actions were PPARγ-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-κB (NF-κB). 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.

View Figures

View References

1	Shen DF, Chang MA, Matteson DM, Buggage R, Kozhich AT and Chan CC: Biphasic ocular inflammatory response to endotoxin-induced uveitis in mouse. Arch Ophthalmol. 118:521–527. 2000. View Article : Google Scholar : PubMed/NCBI
2	Joussen AM, Poulaki V, Le M, et al: A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 18:1450–1452. 2004.PubMed/NCBI
3	Rodrigues EB: Inflammation in dry age-related macular degeneration. Ophthalmologica. 221:143–152. 2007. View Article : Google Scholar : PubMed/NCBI
4	Strauss O: The retinal pigment epithelium in visual function. Physiol Rev. 85:845–881. 2005. View Article : Google Scholar : PubMed/NCBI
5	Kumaki N, Anderson DM, Cosman D and Kumaki S: Expression of interleukin-15 and its receptor by human fetal retinal pigment epithelial cells. Curr Eye Res. 15:876–882. 1996. View Article : Google Scholar : PubMed/NCBI
6	McLaren MJ: Kinetics of rod outer segment phagocytosis by cultured retinal pigment epithelial cells. Relationship to cell morphology. Invest Ophthalmol Vis Sci. 37:1213–1224. 1996.PubMed/NCBI
7	Yu FS and Hazlett LD: Toll-like receptors and the eye. Invest Ophthalmol Vis Sci. 47:1255–1263. 2006. View Article : Google Scholar : PubMed/NCBI
8	Ishii S and Shimizu T: Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog Lipid Res. 39:41–82. 2000. View Article : Google Scholar : PubMed/NCBI
9	Han SJ, Choi JH, Ko HM, et al: Glucocorticoids prevent NF-kappaB activation by inhibiting the early release of platelet-activating factor in response to lipopolysaccharide. Eur J Immunol. 29:1334–1341. 1999. View Article : Google Scholar : PubMed/NCBI
10	Camussi G, Tetta C and Baglioni C: The role of platelet activating factor in inflammation. Clin Immun Immunopathol. 57:331–338. 1990. View Article : Google Scholar : PubMed/NCBI
11	Lotner GZ, Lynch JM, Betz SJ and Henson PM: Human neutrophil-derived platelet activating factor. J Immunol. 124:676–684. 1980.PubMed/NCBI
12	Triggiani M, Schleimer RP, Warner JA and Chilton FH: Differential synthesis of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine and platelet-activating factor by human inflammatory cells. J Immunol. 147:660–666. 1991.PubMed/NCBI
13	Sumita C, Maeda M, Fujio Y, et al: Pioglitazone induces plasma platelet activating factor-acetylhydrolase and inhibits platelet activating factor-mediated cytoskeletal reorganization in macrophage. Biochim Biophys Acta. 1673:115–121. 2004. View Article : Google Scholar
14	Tjoelker LW, Wilder C, Eberhardt C, et al: Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature. 374:549–553. 1995. View Article : Google Scholar : PubMed/NCBI
15	Tontonoz P, Nagy L, Alvarez JG, Thomazy VA and Evans RM: PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 93:241–252. 1998.
16	Mueller E, Sarraf P, Tontonoz P, et al: Terminal differentiation of human breast cancer through PPARγ. Mol Cell. 1:465–470. 1998.
17	Buckingham RE: Thiazolidinediones: pleiotropic drugs with potent anti-inflammatory properties for tissue protection. Hepatol Res. 33:167–170. 2005. View Article : Google Scholar : PubMed/NCBI
18	Consoli A and Devangelio E: Thiazolidinediones and inflammation. Lupus. 14:794–797. 2005. View Article : Google Scholar : PubMed/NCBI
19	Drew PD and Chavis JA: The cyclopentone prostaglandin 15-deoxy-δ^12,14 prostaglandin J₂ represses nitric oxide, TNF-, and IL-12 production by microglial cells. J Neuroimmunol. 115:28–35. 2001.
20	Garg TK and Chang JY: Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: prevention of cell death by AG126 and 15-deoxy-delta^12,14-PGJ₂. BMC Ophthalmol. 3:52003. View Article : Google Scholar : PubMed/NCBI
21	Surh YJ, Na HK, Park JM, et al: 15-Deoxy-Δ^12,14-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling. Biochem Pharmacol. 82:1335–1351. 2011.
22	Abdelrahman M, Sivarajah A and Thiemermann C: Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock. Cardiovasc Res. 65:772–781. 2005. View Article : Google Scholar : PubMed/NCBI
23	Rosenbaum JT, Angell E, Wilson D, Broquet C, Boney RS and Braquet P: Intravitreally injected platelet activating factor induces retinitis in experimental animals. Curr Eye Res. 18:342–348. 1999. View Article : Google Scholar : PubMed/NCBI
24	Bulger EM, Arbabi S, Garcia I and Maier RV: The macrophage response to endotoxin requires platelet activating factor. Shock. 17:173–179. 2002. View Article : Google Scholar : PubMed/NCBI
25	Cousin SW, Guss RB, Howes EL Jr and Rosenbaum JT: Endotoxin-induced uveitis in the rat: observations on alters vascular permeability, clinical findings and histology. Exp Eye Res. 35:665–676. 1984. View Article : Google Scholar : PubMed/NCBI
26	Suzuki M, Noda K, Kubota S, et al: Eicosapentaenoic acid suppresses ocular inflammation in endotoxin-induced uveitis. Mol Vis. 16:1382–1388. 2010.PubMed/NCBI
27	Leung KW, Barnstable CJ and Tombran-Tink J: Bacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signaling. Mol Immunol. 46:1374–1386. 2009. View Article : Google Scholar
28	Planck SR, Dang TT, Graves D, Tara D, Ansel JC and Rosenbaum JT: Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin-1. Invest Ophthalmol Vis Sci. 33:78–82. 1992.PubMed/NCBI
29	Feghali CA and Wright TM: Cytokines in acute and chronic inflammation. Front Biosci. 2:d12–d26. 1997.PubMed/NCBI
30	Biswas PS, Banerjee K, Kinchington PR and Rouse BT: Involvement of IL-6 in the paracrine production of VEGF in ocular HSV-1 infection. Exp Eye Res. 82:46–54. 2006. View Article : Google Scholar : PubMed/NCBI
31	De Vos AF, Hoekzema R and Kijlstra A: Cytokines and uveitis, a review. Curr Eye Res. 11:581–597. 1992.PubMed/NCBI
32	Verma MJ, Lloyd A, Rager H, et al: Chemokines in acute anterior uveitis. Curr Eye Res. 16:1202–1208. 1997. View Article : Google Scholar : PubMed/NCBI
33	Nakazawa T, Hisatomi T, Nakazawa C, et al: Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. Proc Natl Acad Sci USA. 104:2425–2430. 2007. View Article : Google Scholar : PubMed/NCBI
34	Kanagawa T, Matsuda S, Mikawa Y, et al: Role of ICAM-1 and LFA-1 in endotoxin-induced uveitis in mice. Jpn J Ophthalmol. 40:174–180. 1996.PubMed/NCBI
35	Tsuji F and Shirasawa E: The role of platelet-activating factor in cell infiltration in endotoxin-induced uveitis in guinea pigs. Curr Eye Res. 17:501–505. 1998. View Article : Google Scholar : PubMed/NCBI
36	Zhang JZ, Cavet ME, VanderMeid KR, Salvador-Silva M, López FJ and Ward KW: BOL-303242-X, a novel selective glucocorticoid receptor agonist, with full anti-inflammatory properties in human ocular cells. Mol Vis. 15:2606–2616. 2009.PubMed/NCBI
37	Rodrigues CE, Sanches TR, Volpini RA, et al: Effects of continuous erythropoietin receptor activator in sepsis-induced acute kidney injury and multi-organ dysfunction. PLoS One. 7:e298932012. View Article : Google Scholar : PubMed/NCBI
38	Straus DS, Pascual G, Li M, et al: 15-deoxy-delta^12,14-prostaglandin J₂ inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci USA. 97:4844–4849. 2000.PubMed/NCBI
39	Inoue H, Tanabe T and Umeson K: Feedback control of cyclooxygenase-2 expression through PPARgamma. J Biol Chem. 275:28028–28032. 2000.PubMed/NCBI
40	Thieringer R, Fenyk-Melody JE, Le Grand CB, et al: Activation of peroxisome proliferator-activated receptor gamma does not inhibit IL-6 or TNF-alpha responses of macrophages to lipopolysaccharide in vitro or in vivo. J Immunol. 164:1046–1054. 2000. View Article : Google Scholar : PubMed/NCBI