Construction of foundation on the function of the immune suppressive sPLA2 and toward its drug discovery

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860051
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: MIKI Yoshimi 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 研究員 (00632499)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 脂質 / ホスホリパーゼ / 抗炎症 / 皮膚疾患 / 免疫 / オメガ3 / 樹状細胞 / マクロファージ

Outline of Final Research Achievements

In this study, we showed that psoriasis was exacerbated in Pla2g2d-null mice, whereas it was ameliorated in Pla2g2d-overexpressing transgenic mice, relative to littermate wild-type mice. These phenotypes were associated with concomitant alterations in the tissue levels of omega-3 polyunsaturated fatty acid (PUFA) metabolites, which had the capacity to reduce the expression of Th17-type cytokines in dendritic cells or lymph node cells. In the context of cancer, however, Pla2g2d deficiency resulted in marked attenuation of skin carcinogenesis, likely because of the augmented anti-tumor immunity. Altogether, these results underscore a general role of sPLA2-IID as an immunosuppressive sPLA2 that allows the microenvironmental lipid balance toward an anti-inflammatory state, exerting beneficial or detrimental impact depending upon distinct pathophysiological contexts in inflammation and cancer.

Free Research Field

脂質生化学