Involvement of the constitutive prostaglandin E synthase cPGES/p23 in expression of an initial prostaglandin E2 inactivating enzyme, 15-PGDH.

Abstract We previously showed that cytosolic prostaglandin (PG) E synthase (cPGES/p23) which isomerizes PGH 2 to PGE 2 , is essential for fetal mouse development. Embryonic fibroblasts derived from cPGES/p23 knockout mice generated higher amounts of PGE 2 in culture supernatants than wild-type-derived cells. In order to elucidate this apparent conflict that absence of PGE 2 synthetic enzyme caused facilitation of PGE 2 biosynthesis, we examined expression of the PGE 2 degrading enzyme in embryonic fibroblasts. We report here that embryonic fibroblasts deficient in cPGES/p23 decreased the expression of the PGE 2 degrading enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which catalyzes the inactivating conversion of the PGE 2 15-OH to a 15-keto group, compared with that of wild-type. In addition, rat fibroblastic 3Y1 cells harboring cPGES/p23 siRNA exhibited lower 15-PGDH expression than mock-transfected cells. Furthermore, forcible expression of cPGES/p23 in 3Y1 cells resulted in facilitation of 15-PGDH promoter activity. These results suggest that the PGE 2 -inactivating pathway is controlled by the PGE 2 biosynthetic enzyme, cPGES/p23.