Regulation of mast cell function by non-canonical lipid pathway

• Project/Area Number: 16K15122
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo (2017); Tokyo Metropolitan Institute of Medical Science (2016)
• Principal Investigator: Taketomi Yoshitaka 東京大学, 大学院医学系研究科, 助教 (40365804)
• Research Collaborator: MURAKAMI Makoto
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マスト細胞 / アレルギー / 脂質代謝 / ホスホリパーゼA2 / 生理活性脂質 / リピドミクス / 分化成熟 / アレルギー応答 / 脂質メディエーター

Outline of Final Research Achievements

Phospholipase A2s (PLA2s) are a group of enzymes that hydrolyze phospholipids to yield fatty acids and lysophospholipids, which serve as precursors for a variety of lipid mediators. It is currently acknowledged that classical lipid mediators such as arachidonic acid metabolites produced by PLA2s modulate mast cell-associated immune response. Moreover, mast cells express a variety of PLA2s or lipid receptors and can alter the release and production of other mediators including histamine, cytokines and chemokines, and thereby homeostatic or pathophysiological responses. Our current studies on newly acknowledged functional aspects of individual PLA2s or lipid receptors in mast cell-mediated immediate-type allergy in relation to non-canonical lipid pathway revealed that (1) the novel regulation of mast cells by a lipid mediator other than classical arachidonate metabolites and (2) the novel PLA2-driven lipid mediator pathway in the regulation of mast cell quality.

Research Products

• [Journal Article] 脂質代謝と喘息. (2018)
  • Author(s): 武富芳隆, 村上誠.
  • Journal Title: 分子呼吸器病 Volume: 22 Pages: 18-21
• [Journal Article] PLA2とアレルギー. (2018)
  • Author(s): 武富芳隆, 村上誠.
  • Journal Title: アレルギー・免疫 Volume: 25 Pages: 44-43
• [Journal Article] Immunological Regulation by Bioactive Lipids (2017)
  • Author(s): Taketomi Y, Murakami M.
  • Journal Title: YAKUGAKU ZASSHI Volume: 137 Issue: 5 Pages: 503-515
  • DOI: 10.1248/yakushi.16-00239-2
  • NAID: 130005631393
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2017-05-01
• [Journal Article] Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation (2017)
  • Author(s): Shimanaka Yuta、Kono Nozomu、Taketomi Yoshitaka、Arita Makoto、Okayama Yoshimichi、Tanaka Yuki、Nishito Yasumasa、Mochizuki Tatsuki、Kusuhara Hiroyuki、Adibekian Alexander、Cravatt Benjamin F、Murakami Makoto、Arai Hiroyuki
  • Journal Title: Nature Medicine Volume: 23 Issue: 11 Pages: 1287-1297
  • DOI: 10.1038/nm.4417
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Group III phospholipase A2 promotes colitis and colorectal cancer (2017)
  • Author(s): Murase R, Taketomi Y, Miki Y, Nishito Y, Saito M, Fukami K, Yamamoto K, Murakami M.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 12261-12261
  • DOI: 10.1038/s41598-017-12434-z
  • NAID: 120006535021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Autotaxin-lysophosphatidic acid-LPA3 signaling at the embryo-epithelial boundary controls decidualization pathways (2017)
  • Author(s): Aikawa Shizu、Kano Kuniyuki、Inoue Asuka、Wang Jiao、Saigusa Daisuke、Nagamatsu Takeshi、Hirota Yasushi、Fujii Tomoyuki、Tsuchiya Soken、Taketomi Yoshitaka、Sugimoto Yukihiko、Murakami Makoto、Arita Makoto、Kurano Makoto、Ikeda Hitoshi、Yatomi Yutaka、Chun Jerold、Aoki Junken
  • Journal Title: EMBO J Volume: 36 Issue: 14 Pages: 2146-2160
  • DOI: 10.15252/embj.201696290
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 脂質代謝による自然免疫・アレルギーの制御 (2017)
  • Author(s): 武富芳隆, 村上誠
  • Journal Title: アレルギーの臨床 Volume: 37 Pages: 58-62
• [Journal Article] Secreted Phospholipase A2 Specificity on Natural Membrane Phospholipids (2017)
  • Author(s): Yamamoto K, Miki Y, Sato H, Murase R, Taketomi Y, Murakami M
  • Journal Title: Methods Enzymol Volume: 583 Pages: 101-117
  • DOI: 10.1016/bs.mie.2016.09.007
  • Peer Reviewed / Open Access
• [Journal Article] Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury (2016)
  • Author(s): Shigematsu, M., Koga, T., Ishimori, A., Saeki, K., Ishii, Y., Taketomi, Y., Ohba, M., Jo-Watanabe, A., Okuno, T., Harada, N., Harayama, T., Shindou, H., Li, J. D., Murakami, M., Hoka, S.,Yokomizo, T.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 34560-34560
  • DOI: 10.1038/srep34560
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis. (2016)
  • Author(s): Tanigawa H, Miyata K, Tian Z, Aoi J, Kadomatsu T, Fukushima S, Ogata A, Takeda N, Zhao J, Zhu S, Terada K, Endo M, Morinaga J, Sugizaki T, Sato M, Morioka MS, Manabe I, Mashimo Y, Hata A, Taketomi Y, Yamamoto K, Murakami M, Araki K, Jinnin M, Ihn H, Oike Y
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 34690-34690
  • DOI: 10.1038/srep34690
  • NAID: 120006534970
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 肥満細胞と脂質メディエーター (2016)
  • Author(s): 武富芳隆, 村上誠
  • Journal Title: 皮膚アレルギーフロンティア Volume: 14 Pages: 19-24
• [Journal Article] Dual Roles of Group IID Phospholipase A2 in Inflammation and Cancer (2016)
  • Author(s): Miki Y, Kidoguchi Y, Sato M, Taketomi Y, Taya C, Muramatsu K, Gelb MH, Yamamoto K, Murakami M
  • Journal Title: J Biol Chem Volume: 291(30) Issue: 30 Pages: 15588-601
  • DOI: 10.1074/jbc.m116.734624
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression and Function of Group IIE Phospholipase A2 in Mouse Skin (2016)
  • Author(s): Yamamoto K, Miki Y, Sato H, Nishito Y, Gelb MH, Taketomi Y, Murakami M
  • Journal Title: J Biol Chem Volume: 291(30) Issue: 30 Pages: 15602-13
  • DOI: 10.1074/jbc.m116.734657
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolic regulation by secreted phospholipase A2. (2016)
  • Author(s): Sato H, Taketomi Y, Murakami M.
  • Journal Title: Inflamm Regener. Volume: 36 Issue: 1 Pages: 1-7
  • DOI: 10.1186/s41232-016-0012-7
  • Peer Reviewed
• [Journal Article] Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility. (2016)
  • Author(s): Murase R, Sato H, Yamamoto K, Ushida A, Nishito Y, Ikeda K, Kobayashi T, Yamamoto T, Taketomi Y, Murakami M.
  • Journal Title: J Biol Chem. Volume: 291 Issue: 13 Pages: 6895-6911
  • DOI: 10.1074/jbc.m116.715672
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 脂質代謝によるアレルギー性疾患制御. (2018)
  • Author(s): 武富芳隆, 村上誠.
  • Organizer: 第2回アレルギー治療updateフォーラム
  • Invited
• [Presentation] 脂質代謝によるアレルギー性疾患の制御. (2018)
  • Author(s): 武富芳隆, 村上誠.
  • Organizer: 三重ビラノア錠発売1周年記念講演会
  • Invited
• [Presentation] 脂質代謝による炎症・アレルギーの制御. (2017)
  • Author(s): 武富芳隆, 村上誠.
  • Organizer: 第41回星薬科大学大学院研究科助手会・大学院自治会合同公開セミナー
  • Invited
• [Presentation] 生理活性脂質代謝と免疫アレルギー疾患. (2017)
  • Author(s): 武富芳隆, 村上誠.
  • Organizer: 第19回応用薬理シンポジウム
  • Invited
• [Presentation] アレルギーと脂質メディエーター. (2017)
  • Author(s): 武富芳隆, 村上誠.
  • Organizer: 第22回那須ティーチイン
  • Invited
• [Presentation] 表皮の脂質代謝とアレルギー疾患. (2017)
  • Author(s): 武富芳隆, 村上誠.
  • Organizer: 第38回日本炎症・再生医学会
  • Invited
• [Presentation] 生理活性脂質による炎症・アレルギーの制御. (2017)
  • Author(s): 武富芳隆, 村上誠.
  • Organizer: 第66回日本アレルギー学会
  • Invited
• [Presentation] III型分泌性ホスホリパーゼ A2は動脈硬化の新規増悪因子である (2016)
  • Author(s): 武富芳隆, 宮崎拓郎, 三木寿美, 佐藤弘泰, 村上誠
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2016-09-25
• [Presentation] 脂質によるアレルギー制御の新機軸 (2016)
  • Author(s): 武富芳隆, 村上誠
  • Organizer: 第65回日本アレルギー学会
  • Place of Presentation: 東京国際フォーラム (東京都千代田区)
  • Year and Date: 2016-06-17
  • Invited
• [Presentation] マスト細胞を制御する第二のAnaphylactic sPLA2の同定 (2016)
  • Author(s): 武富芳隆, 砂川アンナ, 入江敦, 山本圭, 三木寿美, 佐藤弘泰, 小林哲幸, 村上誠
  • Organizer: 第58回日本脂質生化学会
  • Place of Presentation: にぎわい交流館AU (秋田県秋田市)
  • Year and Date: 2016-06-09
• [Presentation] 脂質代謝による免疫アレルギー疾患制御の新機軸 (2016)
  • Author(s): 武富芳隆
  • Organizer: 第5回TOBIRA交流研究フォーラム
  • Place of Presentation: ソラシティ カンファレンスセンター (東京千代田区)
  • Year and Date: 2016-05-23
• [Remarks] 体に優しいオメガ3脂肪酸の意外な側面：オメガ3脂肪酸を動かしてアレルギーを促す酵素の発見.
  • URL: http://www.amed.go.jp/news/release_20171010-01.html
• [Remarks] エポキシ化3脂肪酸は免疫グロブリンEに依存的なマスト細胞の活性化を制御する.
  • URL: http://first.lifesciencedb.jp/archives/17335#more-17335
• [Remarks] 東京都医学総合研究所 脂質代謝プロジェクト
  • URL: http://www.igakuken.or.jp/project/detail/lipid.html