Background: Psoriasis is a chronic inflammatory disease that is accompanied by abnormalities in the immune system. It was recently reported that microsomal prostaglandin E synthase-1 (mPGES-1), a terminal enzyme for PGE₂ 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.

Methods: Psoriasis-like skin inflammation was induced in mice lacking mPGES-1 (mPGES-1^−/− mice) and wild-type (WT) mice by administrating IMQ under specific pathogen free condition. The expressions of mPGES-1 mRNA and protein in the skin were determined by real-time PCR and western blotting, respectively. The skin inflammation was evaluated based on scores with macroscopic symptoms and histological features. In addition, the expression levels of intereukin-17A (IL-17A) in inflamed skin was determined by real-time PCR.

Results: The expression of mPGES-1 was highly induced on both mRNA and protein levels in the skin of WT mice after IMQ administration. Interestingly, the mPGES-1^−/− mice exhibited more severe symptoms of psoriasis-like skin inflammation compared to those of WT mice during administration of IMQ. Histological analysis further showed significant increase of epidermal thickness in mPGES-1^−/− mice. The skin expression of IL-17A, a prominent target for the treatment of psoriasis, was highly up-regulated in mPGES-1^−/− mice in response to IMQ administration.

Conclusion: mPGES-1/PGE₂ system plays a protective role in psoriasis, partly by reducing the expression of IL-17A.