Background)
Microsomal prostaglandin (PG) E synthase 1 (mPGES-1) is an inducible enzyme downstream of COX-2 in PGE₂ biosynthesis. We have reported that Aspirin inhibited angiogenesis by suppressing regulatory T cells (Tregs) accumulation. Base on this, we hypothesized that mPGES-1 induces angiogenesis and 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. Polyurethane sponge disks were implanted into dorsal subcutaneous tissue of mice. Angiogenesis was estimated by weight of granulation tissues and expression of Vascular Endothelial Growth Factor (VEGF) and CD31 were estimated by real time -PCR. Contribution of Tregs was estimated by immunohistochemical analysis and real time PCR against Forkhead boxoprotein P3 (FOXP3) specific transcript factor for Tregs.
Results)
Compared to WT, weight of granulation tissue was significantly suppressed in mPges-1^-/- (P<0.05). Expression of CD31 and VEGF were suppressed in mPges-1^-/--. The expression of FOXP3 in the granulation tissue was significantly suppressed in mPges-1^-/- compared to WT (P<0.05). Those numbers of FOXP3 positive cells were also impaired in mPges-1^-/-- Compared to WT. Furthermore, by using real time PCR and immunohistochemical analysis the expression of Transforming Growth Factor-β (TGF-b), one of the major cytokine secreted from Tregs, was significantly decreased in mPges-1^-/-.
Conclusion)
These results suggested that mPGES-1/PGE₂ axis induces granulation formation by accumulating Tregs.