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목적 : To investigate the pathogenic role of sphingosine-1-phosphate (S1P) in an in vitro model of Graves’ orbitopathy (GO)
방법 : S1P receptor (SIPR) 1-5 mRNA genes were identified and compared between non-GO and GO orbital tissues using real time PCR. Cell viability of GO cells by addition of S1P was investigated using MTT assay. After cells were treated with S1P of variable concentrations, proinflammatory molecules of IL-6, IL-8, COX2 and ICAM-1 proteins were analyzed using western blot analyses. Effect of S1P was found on adipogenesis using oil-red O staina and western blot analysis regarding PPAR, C/EBP and β.
결과 : S1P receptor 1-3 mRNA level was significantly higher in GO tissues than in non-GO tissues(p<0.05), however S1PR 4 and 5 were lower in GO tissues. Cell viability was not affected by S1P treatment. Proinflammatory molecules were upregulated by S1P in a dose-dependent manner. IL-1β-induced COX-2 protein, increased by addition of S1P were suppressed by S1P antagonist. Treatment of cells with S1P increased pERK and ERK inhibitor significantly blocked S1P induced COX-2 upregulation. S1P significantly increased oil red O stained cells and transcriptional regulators including PPARγ, C/EBPα and β.
결론 : S1P was associated in inflammation and adipogenesis of GO orbital fibroblast, suggesting a possible pathogenic role of S1P in GO.
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