Role of microsomal prostaglandin E synthase-1 in skin inflammation and T-cell immune response of imiquimod-induced psoriasis in mice.

Abstract

Psoriasis is a chronic inflammatory disease associated with abnormalities in the immune system. Microsomal prostaglandin E synthase-1 (mPGES-1), a terminal enzyme for prostaglandin (PG) E₂ biosynthesis, highly expresses in the skin of psoriasis patients. However, the detailed role of mPGES-1 in psoriasis remains unclear. In this study, we investigated the role of mPGES-1 in psoriasis-like skin inflammation induced by imiquimod (IMQ), one of the well-established models of psoriasis. Psoriasis-like skin inflammation was induced in mice lacking mPGES-1 (mPGES-1^−/− mice) and wild-type (WT) mice by administrating IMQ. The expressions of mPGES-1 mRNA and protein were highly induced in WT skin by IMQ, which correlated to the increase of skin PGE₂. The production of PGE₂ was abolished in mPGES-1^−/− skin, indicating that mPGES-1 is a responsible enzyme for skin PGE₂ production. Interestingly, mPGES-1^−/− mice exhibited severer symptoms of psoriasis compared to those of WT mice, indicating the protective role of mPGES-1 in the development of psoriasis. In addition, the skin expression of IL-17A, an aggravating factor for psoriasis, was significantly higher in mPGES-1^−/− mice compared to WT mice in response to IMQ. Furthermore, compared with WT mice, the number of IL-17A-producing TCRβ⁺ cells was significantly increased in mPGES-1^−/− skin, suggesting an importance of mPGES-1 in the IL-17A-related T-cell immune response. Taken together, mPGES-1/PGE₂ system plays a protective role in psoriasis, partly by regulating T-cell immune response associated with IL-17A.