Lipid mediators and mast cells are involved in M2 macrophage accumulation and spinal injury repair

• Project/Area Number: 26670030
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: Sugimoto Yukihiko 熊本大学, 大学院生命科学研究部(薬), 教授 (80243038)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: プロスタグランジン / M2マクロファージ / 脊髄損傷 / 脈絡叢 / マスト細胞 / ケモカイン / マクロファージ / 分化

Outline of Final Research Achievements

In spinal injury, the peripheral macrophages enter into injured sites. It has been shown that M1 and M2 pass through spinal blood vessels and choroid plexus, respectively. M2 differentiation occurs when peripheral macrophages pass through choroid plexus, and such accumulated M2 cells play roles in injury repair. Based on the previously obtained results, we hypothesized that mast cells around the choroid plexus regulate M2 differentiation and spinal repair in a lipid mediator-dependent manner and explored it. We obtained data suggesting involvement of mast cells and prostaglandin in these processes.

Research Products

• [Journal Article] Cross-talk between prostaglandin and retinoic acid signaling. (2018)
  • Author(s): Inazumi, T., and Sugimoto, Y.
  • Journal Title: Carotenoid Sci. Volume: 23
  • Peer Reviewed
• [Journal Article] ゼブラフィッシュにおけるプロスタグランジンシステム (2018)
  • Author(s): 土屋創健、杉本幸彦
  • Journal Title: 生化学 Volume: 89 Pages: 445-445
  • NAID: 40021265217
  • Peer Reviewed
• [Journal Article] プロスタグランジンE2による炎症病態制御機構 (2018)
  • Author(s): 稲住知明、杉本幸彦
  • Journal Title: 細胞 Volume: 50 Pages: 118-121
• [Journal Article] リポクオリティの違いに基づくプロスタノイドのがん疾患制御 (2018)
  • Author(s): 土屋創健、杉本幸彦
  • Journal Title: 実験医学 Volume: 印刷中
• [Journal Article] Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL-induced formation of multinuclear osteoclasts (2017)
  • Author(s): Kato Hikaru、Kai Aika、Kawabata Tetsuro、Sunderhaus James D.、McAfoos Timothy J.、Finefield Jennifer M.、Sugimoto Yukihiko、Williams Robert M.、Tsukamoto Sachiko
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 27 Issue: 22 Pages: 4975-4978
  • DOI: 10.1016/j.bmcl.2017.10.017
  • NAID: 120006897984
  • 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
  • DOI: 10.15252/embj.201696290
  • URL: https://pure.teikyo.jp/en/publications/9eff2a14-8b59-4329-98bc-70cc556391fc
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An aromatic amino acid within intracellular loop 2 of the prostaglandin EP2 receptor is a prerequisite for selective association and activation of Gαs. (2017)
  • Author(s): Yano A, Takahashi Y, Moriguchi H, Inazumi T, Koga T, Otaka A, Sugimoto Y.
  • Journal Title: Biochim Biophys Acta Mol Cell Biol Lipids Volume: 1862 Issue: 6 Pages: 615-622
  • DOI: 10.1016/j.bbalip.2017.03.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. (2017)
  • Author(s): Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, Ozawa T, Nakamura M, Kumagai M, Watashi K, Taketo M, Aoki T, Narumiya S, Oshima M, Arita M, Hara E, Ohtani N.
  • Journal Title: Cancer Discov Volume: in press Issue: 5 Pages: 522-538
  • DOI: 10.1158/2159-8290.cd-16-0932
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 雌性生殖生理におけるプロスタグランジン受容体の役割 (2017)
  • Author(s): 杉本幸彦
  • Journal Title: 別冊BIO Clinica 慢性炎症と疾患 Volume: 6 Pages: 16-21
• [Journal Article] Prostaglandin D2 elicits the reversible neurite retraction in hypothalamic cell line. (2016)
  • Author(s): Tsuchiya H, Hohjoh H, Fujiwara Y, Sugimoto Y, Koshimizu TA.
  • Journal Title: Biochem Biophys Res Commun. Volume: 470 Issue: 4 Pages: 804-810
  • DOI: 10.1016/j.bbrc.2016.01.091
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Olfactory receptor for prostaglandin F2α mediates male fish courtship behavior. (2016)
  • Author(s): Yabuki Y, Koide T, Miyasaka N, Wakisaka N, Masuda M, Ohkura M, Nakai J, Tsuge K, Tsuchiya S, Sugimoto Y, Yoshihara Y
  • Journal Title: Nature Neuroscience Volume: 19 Issue: 7 Pages: 897-904
  • DOI: 10.1038/nn.4314
  • Peer Reviewed / Open Access
• [Journal Article] プロスタノイド受容体を介した免疫・炎症応答亢進の分子機構 (2016)
  • Author(s): 告恭史郎、杉本幸彦
  • Journal Title: 医学のあゆみ Volume: 256 Pages: 561-566
• [Journal Article] プロスタノイドクオリティと心血管系制御 (2016)
  • Author(s): 告恭史郎、稲住知明、杉本幸彦
  • Journal Title: 血管医学 Volume: 17 Pages: 37-43
• [Journal Article] プロスタノイド受容体を介した免疫・炎症応答亢進の分子機構 (2016)
  • Author(s): 告恭史郎, 杉本幸彦
  • Journal Title: 医学のあゆみ Volume: 256(5) Pages: 561-566
• [Journal Article] Prostaglandin E2-induced inflammation: relevance of prostaglandin E receptors. (2015)
  • Author(s): Kawahara K, Hohjoh H, Inazumi T, Tsuchiya S, Sugimoto Y
  • Journal Title: Biochim Biophys Acta Volume: 1851 Issue: 4 Pages: 414-421
  • DOI: 10.1016/j.bbalip.2014.07.008
  • Peer Reviewed / Open Access
• [Journal Article] Dermal Vγ4(+) γδ T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8(+) T-Cell Activity through TNF-α Production. (2015)
  • Author(s): Nakamizo S, Egawa G, Tomura M, Sakai S, Tsuchiya S, Kitoh A, Honda T, Otsuka A, Nakajima S, Dainichi T, Tanizaki H, Mitsuyama M, Sugimoto Y, Kawai K, Yoshikai Y, Miyachi Y, Kabashima K.
  • Journal Title: Journal of Investigative Dermatology Volume: 135 Issue: 4 Pages: 1007-1015
  • DOI: 10.1038/jid.2014.516
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] p13 overexpression in pancreatic b-cells ameliorates type 2 diabetes in high-fat-fed mice (2015)
  • Author(s): Higashi, S. et al.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 461 Issue: 4 Pages: 612-617
  • DOI: 10.1016/j.bbrc.2015.04.074
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative gene expression profiles in pancreatic islets associated with agouti yellow mutation and PACAP overexpression in mice (2015)
  • Author(s): Ikeda K, Tomimoto S, Tsuchiya S, Hamagami K, Shintani N, Sugimoto Y, Ichikawa A, Kasai A, Nakazawa T, Nagayasu K, Hayata-Takano A, Baba A, Hashimoto H
  • Journal Title: Biochim Biophys Rep Volume: 2 Pages: 179-183
  • DOI: 10.1016/j.bbrep.2015.06.006
  • Peer Reviewed / Open Access
• [Journal Article] Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling that Drives Tumor Growth, Angiogenesis and Metastasis. (2015)
  • Author(s): Inada M, Takita M, Yokoyama S, Watanabe K, Tominari T, Matsumoto C, Hirata M, Maru Y, Maruyama T, Sugimoto Y, Narumiya S, Uematsu S, Akira S, Murphy G, Nagase H, Miyaura C.
  • Journal Title: J Biol Chem. Volume: 290 Issue: 50 Pages: 29781-93
  • DOI: 10.1074/jbc.m115.669481
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] プロスタグランジンによる皮膚マスト細胞の成熟と活性化 (2015)
  • Author(s): 杉本幸彦
  • Journal Title: 臨床免疫・アレルギー科 Volume: 63 Pages: 62-67
  • NAID: 40020330437
• [Journal Article] 炎症反応におけるプロスタグランジンE2の役割 (2015)
  • Author(s): 岩崎亮, 北條寛典, 杉本幸彦
  • Journal Title: 細胞 Volume: 47 Pages: 266-269
• [Journal Article] 急性炎症にかかわるプロスタグランジンとその働き (2015)
  • Author(s): 杉本幸彦
  • Journal Title: 医学のあゆみ Volume: 254（12） Pages: 1091-1096
• [Journal Article] Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin. (2014)
  • Author(s): Natsuaki Y, Egawa G, Nakamizo S, Ono S, Hanakawa S, Okada T, Kusuba N, Otsuka A, Kitoh A, Honda T, Nakajima S, Tsuchiya S, Sugimoto Y, Ishii KJ, Tsutsui H, Yagita H, Iwakura Y, Kubo M, Ng Lg, Hashimoto T, Fuentes J, Guttman-Yassky E, Miyachi Y, Kabashima K
  • Journal Title: Nature Immunology Volume: 15 Issue: 11 Pages: 1064-9
  • DOI: 10.1038/ni.2992
  • Peer Reviewed
• [Journal Article] Eosinophils control the resolution of inflammation and draining lymph node hypertrophy through the proresolving mediators and CXCL13 pathway in mice (2014)
  • Author(s): Tani Y, Arita M, Isobe Y, Imoto Y, Segi-Nishida E, Sugimoto Y, Arai H
  • Journal Title: FASEB J Volume: 28 Issue: 9 Pages: 4036
  • DOI: 10.1096/fj.14-251132
  • URL: https://pure.teikyo.jp/en/publications/f0527d31-a3c1-4281-a535-329fb99be967
  • Peer Reviewed / Open Access
• [Journal Article] 12-hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor. (2014)
  • Author(s): Liu M, Saeki K, Matsunobu T, Okuno T, Koga T, Sugimoto Y, Yokoyama C, Nakamizo S, Kabashima K, Narumiya S, Shimizu T, Yokomizo T
  • Journal Title: J Exp Med Volume: 211 Issue: 6 Pages: 1063-1078
  • DOI: 10.1084/jem.20132063
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] プロスタグランジンEP4受容体による脂質代謝調節機構 (2017)
  • Author(s): 杉本幸彦
  • Organizer: 第90回日本内分泌学会
• [Presentation] 旧くて新しいプロスタグランジンの生理機能 (2017)
  • Author(s): 杉本幸彦
  • Organizer: 第41回蛋白質と酵素の構造と機能に関する九州シンポジウム
  • Invited
• [Presentation] プロスタグランジン受容体による生理と病態の調節機構 (2017)
  • Author(s): 杉本幸彦
  • Organizer: 第31回カロテノイド研究談話会
  • Invited
• [Presentation] Prostaglandin E2 regulates physiological lipid storage status (2017)
  • Author(s): Yukihiko Sugimoto
  • Organizer: 15th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
  • Int'l Joint Research
• [Presentation] Regulation of adipocyte functions by the prostaglandin EP4 receptor -Lipid regulates the lipid storage balance- (2017)
  • Author(s): Yukihiko Sugimoto
  • Organizer: The 1st International Conference on Lipoquality
  • Int'l Joint Research / Invited
• [Presentation] 雌性生殖生理におけるプロスタグランジンの役割 (2017)
  • Author(s): 杉本幸彦
  • Organizer: 2017年度生命科学系学会合同年次大会（ConBio2017）
  • Invited
• [Presentation] マスト細胞の炎症性応答に対するプロスタサイクリン受容体IPの抑制機構 (2017)
  • Author(s): 宮本卓馬，鈴木佑治，渡辺真由帆，森本和志，村上里穂，稲住知明，土屋創健，成宮周，杉本幸彦
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター（仙台市）
• [Presentation] オス特異的神経回路形成におけるPGE2-EP受容体の役割 (2017)
  • Author(s): 北條寛典，吉岡美樹，平川昌樹，土屋裕義，土屋創健，瀬木-西田恵里，杉本幸彦
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール（長崎市）
• [Presentation] IL-33によるマスト細胞の炎症性サイトカイン産生におけるプロスタサイクリン受容体IPの役割 (2016)
  • Author(s): 宮本卓馬, 鈴木佑治, 渡辺真由帆, 森本和志, 稲住知明, 土屋創健, 成宮周, 杉本幸彦
  • Organizer: 日本薬学会 第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] プロスタサイクリンIP受容体がマスト細胞炎症性応答に与える影響 (2016)
  • Author(s): 村上里穂，宮本卓馬，鈴木佑治，渡辺真由帆，森本和志，稲住知明，土屋創健，成宮周，杉本幸彦
  • Organizer: 第33回日本薬学会九州支部大会
  • Place of Presentation: 鹿児島大学（鹿児島市）
• [Presentation] PGE2-EP3 receptor signaling induces inflammatory swelling by mast cell activation (2016)
  • Author(s): Yukihiko Sugimoto
  • Organizer: PSK-PSJ joint-international symposium in 2016（日韓薬学会共同国際シンポジウム）
  • Place of Presentation: The K Hotel Seoul（Seoul, Korea）
  • Int'l Joint Research / Invited
• [Presentation] プロスタグランジンE受容体による脳のオス化の分子機構 (2016)
  • Author(s): 北條寛典，吉岡美樹，平川昌樹，土屋裕義，土屋創健，三隅将吾，瀬木-西田恵里，杉本幸彦
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（仙台市）
• [Presentation] マスト細胞の炎症性応答に対するプロスタサイクリン受容体IPの役割 (2016)
  • Author(s): 宮本卓馬，鈴木佑治，渡辺真由帆，森本和志，土屋創健，成宮周，杉本幸彦
  • Organizer: 第15回次世代を担う若手ファーマ・バイオフォーラム
  • Place of Presentation: 大阪大学薬学研究科（大阪府吹田市）
• [Presentation] プロスタノイドIP受容体によるマスト細胞の炎症性応答の抑制機構 (2016)
  • Author(s): 宮本卓馬，鈴木佑治，渡辺真由帆，森本和志，土屋創健，成宮周，杉本幸彦
  • Organizer: 日本生化学会九州支部例会
  • Place of Presentation: 鹿児島大学（鹿児島市）
• [Presentation] IL-33誘導性マスト細胞応答におけるプロスタサイクリン受容体IPの役割 (2015)
  • Author(s): 宮本卓馬, 鈴木佑治, 渡辺真由帆, 森本和志, 土屋創健, 成宮周, 杉本幸彦
  • Organizer: 第88回日本生化学会大会（BMB2015）
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] プロスタグランジンI2によるマスト細胞応答の制御 (2015)
  • Author(s): 宮本卓馬, 鈴木佑治, ○村上里穂, 渡辺真由帆, 森本和志, 稲住知明, 土屋創健, 杉本幸彦
  • Organizer: 第37回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2015-11-19
• [Presentation] プロスタグランジンE2による皮膚炎症惹起の分子機構 (2015)
  • Author(s): 杉本幸彦
  • Organizer: 第19回日本ヒスタミン学会
  • Place of Presentation: 仙台
  • Year and Date: 2015-11-13
  • Invited
• [Presentation] プロスタグランジンの炎症作用:生理と病態を繋ぐもの (2015)
  • Author(s): 杉本幸彦
  • Organizer: 第22回日本血液代替物学会年次大会
  • Place of Presentation: 熊本
  • Year and Date: 2015-10-22
  • Invited
• [Presentation] Roles of prostaglandin E2 in acute inflammation of skin (2015)
  • Author(s): Sugimoto Y, Tsuchiya S, Inazumi T, Narumiya S
  • Organizer: The 14th International conference on Bioactive Lipids in cancer, inflammation and related diseases
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2015-07-12
  • Int'l Joint Research
• [Presentation] Prostaglandin E2 - EP3 signaling triggers mast cell activation and acute inflammation. (2015)
  • Author(s): Sugimoto Y
  • Organizer: 6th International Conference on Phospholipase A2 and Lipid Mediators (PLM2015)
  • Place of Presentation: Tokyo
  • Year and Date: 2015-02-10 – 2015-02-12
  • Invited
• [Presentation] Prostaglandin E2 - EP3 signaling triggers acute inflammation by mast cell activation (2014)
  • Author(s): Sugimoto Y
  • Organizer: 5th European Workshop on Lipid Mediators
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2014-10-23 – 2014-10-24
  • Invited
• [Presentation] プロスタサイクリン受容体IPによるIL-33誘導性サイトカイン産生の抑制メカニズム (2014)
  • Author(s): 鈴木 佑治, 渡辺 真由帆, 森本 和志, 土屋 創健, 杉本 幸彦
  • Organizer: 第13回次世代を担う若手ファーマ・バイオフォーラム2014
  • Place of Presentation: 富山
  • Year and Date: 2014-09-19 – 2014-09-20
• [Remarks]
  • URL: http://www.pharm.kumamoto-u.ac.jp/Labs/seika/index.html
• [Patent(Industrial Property Rights)] 抗がん剤 (2017)
  • Inventor(s): 土屋創健、村山裕海、杉本幸彦
  • Industrial Property Rights Holder: 国立大学法人熊本大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-193596
  • Filing Date: 2017
• [Patent(Industrial Property Rights)] 抗がん剤 (2017)
  • Inventor(s): 土屋創健、村山裕海、杉本幸彦
  • Industrial Property Rights Holder: 国立大学法人熊本大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-193597
  • Filing Date: 2017