Role of Prostaglandin Synthases in chemical-induced skin diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18909
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Showa University
• Principal Investigator: Sasaki Yuka 昭和大学, 薬学部, 助教 (40635108)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: プロスタグランジン / プロスタサイクリン / 接触性皮膚炎 / 皮膚発がん / mPGES-1 / PGIS

Outline of Final Research Achievements

Prostacyclin Synthase (PGIS) and microsomal Prostaglandin E2 Synthase (mPGES)-1 are terminal enzymes that act downstream of cyclooxygenase (COX)-2 in the PGI2 and PGE2-biosynthetic pathway, respectively. In this study, we analyzed the role of PGIS and mPGES-1 in skin dermatitis and skin carcinogenesis. Both in PGIS knockout (KO) mice and mPGES-1 KO mice, DNFB (dinitrofluorobenzene) induced contact hypersensitivity was suppressed than that of WT mice. We performed immunohistochemical analysis. mPGES-1 expressed in keratinocytes and leukocytes and PGIS expressed in vascular cells. Next, we examined role of mPGES-1 and PGIS in 7, 12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol acetate (TPA)-induced two-steps skin carcinogenesis. Formation of papillomas induced by DMBA/TPA was suppressed in mPGES-1 KO mice, compared to WT mice. On the other hands, DMBA/TPA-induced papilloma formation was increased in mPGES-1/PGIS double KO mice, compared to mPGES-1 KO mice.

Free Research Field

衛生薬学