肉芽組織形成を促進するmPGES-1/PGE2経路の役割

• Published in: 日本薬理学会年会要旨集 p. 2-P2-34
• Main Authors: 兵頭, 徹也, 畑中, 公, 伊藤, 義也, 江島, 耕二, 審良, 静男, 天野, 英樹, 細野, 加奈子, 武田, 啓, 植松, 智
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: arachidonic acid; prostaglandin; T-cell; transforming growth factor
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_2-P2-34

Background)Microsomal prostaglandin (PG) E synthase 1 (mPGES-1) is an inducible enzymedownstream of COX-2 in PGE2 biosynthesis. We have reported thatAspirin inhibited angiogenesis by suppressing regulatory T cells (Tregs)accumulation. Base on this, we hypothesized that mPGES-1 induces angiogenesisand granulation tissue formation by Tregs accumulation.Material and Methods) Male 6-8 week-old wild-type (WT) mice and mPGES-1-deficient(mPges-1-/-) mice. Polyurethanesponge disks were implanted into dorsal subcutaneous tissue ofmice. Angiogenesis was estimated by weight of granulation tissues and expressionof Vascular Endothelial Growth Factor (VEGF) and CD31 were estimated by realtime -PCR. Contribution of Tregs was estimated by immunohistochemical analysisand real time PCR against Forkhead boxoprotein P3 (FOXP3) specific transcriptfactor for Tregs.Results) Compared to WT, weight of granulation tissue was significantly suppressed inmPges-1-/- (P<0.05).Expression of CD31 and VEGF were suppressed inmPges-1-/--. The expressionof FOXP3 in the granulation tissue was significantly suppressed inmPges-1-/- compared to WT(P<0.05). Those numbers of FOXP3 positive cells were also impaired inmPges-1-/-- Compared to WT.Furthermore, by using real time PCR and immunohistochemical analysis theexpression of Transforming Growth Factor-β (TGF-b), one of the major cytokinesecreted from Tregs, was significantly decreased inmPges-1-/-.Conclusion) These results suggested that mPGES-1/PGE2 axis induces granulationformation by accumulating Tregs.