Effect of Prostaglandin E_2 and EP Receptor Agonists on Cell Proliferation and Basic Fibroblast Growth Factor Synthesis of Rheumatoid Synovial Fibroblasts in Vitro

概要

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The role of prostaglandin E_2 in inflammatory process is still elusive. We have studied the effect of prostaglandin E_2 on rheumatoid synovial fibroblast proliferation and synthesis of basic fibroblast growth factor in vitro. When synovial fibroblasts were cultured for 72 hours in the presence of prostaglandin E_2, over 10^<-10> M of prostaglandin E_2 has shown significant decrease of tritiated thymidine incorporation in synovial fibroblast monolayer culture. Both EP2 receptor and EP4 receptor agonist also suppressed synovial fibroblast proliferation, whereas EP1 or EP3 receptor agonist failed to affect cell proliferation up to 10^<-6> M. Next, the effect of prostaglandin E_2 on basic fibroblast growth factor mRNA expression of synovial fibroblast was examined. Basic fibroblast growth factor mRNA expression was markedly enhanced when synovial fibroblasts were treated with 10^<-6> M prostaglandin E_2. EP1 receptor agonist has also enhanced basic fibroblast growth factor mRNA induction, whereas EP2, EP3 and EP4 receptor agonist failed to augment mRNA induction of synovial fibroblast. These results suggested that selective EP receptor agonists or antagonists should be utilized in future for treatment of rheumatoid arthritis for preventing pannus formation by EP2/EP4 activation and bone resorption led to joint destruction by EP1 inactivation.
神戸大学の論文
2000-12-27