New insights into the roles of secreted phospholipase A2 in allergy, atherosclerosis, and cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TAKETOMI Yoshitaka 公益財団法人東京都医学総合研究所, 生体分子研究分野, 主席研究員 (40365804)
• Research Collaborator: MURAKAMI Makoto
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 脂質代謝 / アレルギー / 動脈硬化 / 大腸癌 / ホスホリパーゼA2 / 脂質メディエーター

Outline of Final Research Achievements

Phosholipas A2 (PLA2) is a group of enzyme that hydrolyze the phospholipids to yield fatty acids and lysophospholipids. Here we have found that the paracrine PGD2 circuit driven by PLA2G3, a secreted PLA2 isoform, is a previously unrecognized lipid-orchestrated pathway linked to allergy and uncovers a missing microenvironmental cue underlying the proper maturation of mast cells. In addition to that, we identified the LPA-LPA1 axis as another lipid-orchestrated pathway toward mast cell maturation. Besides the regulation of mast cell and allergy, accumulating evidence suggests that PLA2G3 generally acts as a paracrine coordinator of various pathophysiological events as metabolic disorders and inflammatory bowl diseases. Our results highlight that PLA2G3 is bona fide pro-atherogenic sPLA2 that facilitates atherosclerosis through modifying LDL and promotes colitis and colon cancer by mobilizing lysophospholipids, providing a rationale for PLA2G3 to be a novel drug target of these diseases.

Free Research Field

脂質免疫学、アレルギー学