The in vivo roles of biosynthetic enzyme and receptors for leukotriene B4

• Project/Area Number: 18H02627
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Juntendo University
• Principal Investigator: Yokomizo Takehiko 順天堂大学, 医学(系)研究科(研究院), 教授 (60302840)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 生理活性脂質 / 生体分子 / 遺伝子改変マウス / 炎症性疾患 / 生理活性 / シグナル伝達 / ロイコトリエンB4 / 受容体 / 産生酵素

Outline of Final Research Achievements

The following experiments were conducted to clarify the in vivo roles of the biosynthetic enzyme (LTA4H) and receptors (BLT1 and BLT2) for the biologically active lipid leukotriene B4(LTB4). We generated dendritic cell (DC)-specific BLT1-deficient mice, and LTA4H E297Q knock-in mice lacking only aminopeptidase activity. Using these mice, I obtained the following results 1) I identified dendritic cell subsets defined by BLT1 expression and determined their different roles in inflammatory disease models. BLT1-high DC enhances inflammation by staying at the inflammatory lesion and secreting IL-12, and BLT1-low DC migrates to draining lymph node and stimulates T cell proliferation by secreting IL-2. 2) In LTA4H-deficient mice, thyroid hormone secretion is increased, resulting in a "thin" phenotype, which is dependent on the loss of aminopeptidase activity of LTA4H, not on the loss of LTB4-producing activity. LTA4 aminopeptidase activity somehow inhibits thyroid hormones production/release.

Academic Significance and Societal Importance of the Research Achievements

ロイコトリエンB4は強力な炎症作用を有する生理活性脂質であり、その産生酵素や受容体は炎症性疾患の新規治療標的として注目されている。本研究は主としてロイコトリエンB4関連分子の遺伝子欠損マウスの解析を通じて、炎症性疾患の発症と増悪におけるロイコトリエンB4関連分子の関連を明らかにした研究である。本研究は将来的に、ヒトの炎症性疾患の新規創薬に繋がる可能性をもつ研究である。

Research Products

• [Int'l Joint Research] ハーバード大学/ボストン小児病院(米国)
• [Int'l Joint Research] Heptares Therapuutics(英国)
• [Int'l Joint Research] University of Colorado Denver/Harvard Medical School(米国)
• [Int'l Joint Research] Friedrich-Schiller-University Jena(ドイツ)
• [Int'l Joint Research] ハーバード大学/コーネル大学(米国)
• [Int'l Joint Research] Max Plank研究所(ドイツ)
• [Int'l Joint Research] 上海交通大学(中国)
• [Journal Article] The c‐terminal region of BLT2 restricts its localization to the lateral membrane in a LIN7C‐dependent manner (2021)
  • Author(s): Hara Takuya、Saeki Kazuko、Jinnouchi Hiromi、Kazuno Saiko、Miura Yoshiki、Yokomizo Takehiko
  • Journal Title: The FASEB Journal Volume: 35 Issue: 2 Pages: 21364-21364
  • DOI: 10.1096/fj.202002640r
  • Peer Reviewed
• [Journal Article] Metabolism and biological functions of 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (2021)
  • Author(s): Okuno Toshiaki、Yokomizo Takehiko
  • Journal Title: Prostaglandins & Other Lipid Mediators Volume: 152 Pages: 106502-106502
  • DOI: 10.1016/j.prostaglandins.2020.106502
  • Peer Reviewed
• [Journal Article] Up-regulation of cytosolic prostaglandin E synthase in fetal-membrane and amniotic prostaglandin E2 accumulation in labor (2021)
  • Author(s): Nanase Takahashi, Toshiaki Okuno, Hiroki Fujii, Shintaro Makino, Masaya Takahashi, Mai Ohba, Kazuko Saeki, Atsuo Itakura, Satoru Takeda, Takehiko Yokomizo
  • Journal Title: PLoS One Volume: 16 Issue: 4 Pages: e0250638-e0250638
  • DOI: 10.1371/journal.pone.0250638
  • Peer Reviewed / Open Access
• [Journal Article] Liver-specific deletion of Ngly1 causes abnormal nuclear morphology and lipid metabolism under food stress (2020)
  • Author(s): Fujihira Haruhiko、Masahara-Negishi Yuki、Akimoto Yoshihiro、Hirayama Hiroto、Lee Hyeon-Cheol、Story Benjamin A.、Mueller William F.、Jakob Petra、Clauder-M?nster Sandra、Steinmetz Lars M.、Radhakrishnan Senthil K.、Kawakami Hayato、Kamada Yoshihiro、Miyoshi Eiji、Yokomizo Takehiko、Suzuki Tadashi
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Volume: 1866 Issue: 3 Pages: 165588-165588
  • DOI: 10.1016/j.bbadis.2019.165588
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• [Journal Article] Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells (2020)
  • Author(s): Han Bo、Lee‐Okada Hyeon‐Cheol、Ishimine Momoko、Orita Hajime、Nishikawa Keiko、Takagaki Tetsuya、Kajino Kazunori、Yokomizo Takehiko、Hino Okio、Kobayashi Toshiyuki
  • Journal Title: FEBS Open Bio Volume: 10 Issue: 11 Pages: 2375-2387
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  • Peer Reviewed / Open Access
• [Journal Article] Leukotriene B4 receptors as therapeutic targets for ophthalmic diseases (2020)
  • Author(s): Hirakata Toshiaki、Matsuda Akira、Yokomizo Takehiko
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Volume: 1865 Issue: 9 Pages: 158756-158756
  • DOI: 10.1016/j.bbalip.2020.158756
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• [Journal Article] Leukotriene B4 receptor 1 exacerbates inflammation following myocardial infarction. (2020)
  • Author(s): Horii Y, Nakaya M, Ohara H, Nishihara H, Watari K, Nagasaka A, Nakaya T, Sugiura Y, Okuno T, Koga T, Tanaka A, Yokomizo T, Kurose H.
  • Journal Title: FASEB Journal Volume: 印刷中 Issue: 6 Pages: 8749-8763
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  • Peer Reviewed / Open Access
• [Journal Article] The PDK1-FoxO1 Signaling in Adipocytes Controls Systemic Insulin Sensitivity Through the 5-lipoxygenase-leukotriene B 4 Axis (2020)
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• [Journal Article] A novel mutation in the SLCO2A1 gene, encoding a prostaglandin transporter, induces chronic enteropathy. (2020)
  • Author(s): Jimbo K., Okuno T., Ohgaki R., Nishikubo K., Kitamura Y., Sakurai Y., Quan L., Shoji H., Kanai Y., Shimizu T., Yokomizo T
  • Journal Title: PLoS One Volume: 15(11) Issue: 11 Pages: e0241869-e0241869
  • DOI: 10.1371/journal.pone.0241869
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• [Journal Article] Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence. (2020)
  • Author(s): Kaji S, Irino T, Kusuhara M, Makuuchi R, Yamakawa Y, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Kami K, Ohashi Y, Zhang S, Orita H, Lee-Okada HC, Fukunaga T, Terashima M.
  • Journal Title: Gastric Cancer Volume: - Issue: 5 Pages: 874-883
  • DOI: 10.1007/s10120-020-01065-5
  • NAID: 40022329548
  • Peer Reviewed
• [Journal Article] Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation. (2020)
  • Author(s): Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, and Mitsuyoshi Nakao, Takehiko Yokomizo.
  • Journal Title: Cellular & Molecular Immunology Volume: 8 Issue: 6 Pages: 1-13
  • DOI: 10.1038/s41423-020-00559-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Leukotriene A4 hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis. (2020)
  • Author(s): Uzawa H, Kohno D, Koga T, Sasaki T, Fukunaka A, Okuno T, Jo-Watanabe A, Kazuno S, Miyatsuka T, Kitamura T, Fujitani Y, Watada H, Saeki K*, Yokomizo T
  • Journal Title: FASEB J Volume: 34(10) Issue: 10 Pages: 13949-13958
  • DOI: 10.1096/fj.202001148r
  • Peer Reviewed
• [Journal Article] Eicosanoids in Skin Wound Healing. (2020)
  • Author(s): Yasukawa K., Okuno T., Yokomizo T.
  • Journal Title: Int. J. Mol. Sci. Volume: 21(22) Issue: 22 Pages: 8435-8435
  • DOI: 10.3390/ijms21228435
  • Peer Reviewed / Open Access
• [Journal Article] Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition. (2020)
  • Author(s): Ishihara E, Nagaoka Y, Okuno T, Kofuji S, Ishigami-Yuasa M, Kagechika H, Kamimura K, Terai S, Yokomizo T, Sugimoto Y, Fujita Y, Suzuki A, Nishina H.
  • Journal Title: Genes Cells. Volume: 25(3) Issue: 3 Pages: 197-214
  • DOI: 10.1111/gtc.12750
  • NAID: 120006873037
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] n-3 Fatty Acid and Its Metabolite 18-HEPE Ameliorate Retinal Neuronal Cell Dysfunction by Enhancing M?ller BDNF in Diabetic Retinopathy (2020)
  • Author(s): Suzumura Ayana、Kaneko Hiroki、Funahashi Yasuhito、Takayama Kei、Nagaya Masatoshi、Ito Seina、Okuno Toshiaki、Hirakata Toshiaki、Nonobe Norie、Kataoka Keiko、Shimizu Hideyuki、Namba Rina、Yamada Kazuhisa、Ye Fuxiang、Ozawa Yoko、Yokomizo Takehiko、Terasaki Hiroko
  • Journal Title: Diabetes Volume: 69 Issue: 4 Pages: 724-735
  • DOI: 10.2337/db19-0550
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of propofol hydroxyl group in 5-lipoxygenase recognition (2020)
  • Author(s): Yuki Koichi、Bu Weiming、Eckenhoff Roderic G.、Yokomizo Takehiko、Okuno Toshiaki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: In press Issue: 4 Pages: 909-914
  • DOI: 10.1016/j.bbrc.2020.03.037
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Leukotriene B4 receptor type 2 (BLT2) accelerates the healing of intestinal lesions by promoting epithelial cell proliferation (2020)
  • Author(s): Matsumoto Y, Matsuya Y, Kano N, Amagase K, Saeki K, Matsumoto K, Yokomizo T, Kato S
  • Journal Title: Journal of Pharmacology and Experimental Therapeutics Volume: 373 Issue: 1 Pages: 1-9
  • DOI: 10.1124/jpet.119.263145
  • Peer Reviewed
• [Journal Article] Aging exacerbates high‐fat diet‐induced steatohepatitis through alteration in hepatic lipid metabolism in mice (2020)
  • Author(s): Ishizuka Kei、Kon Kazuyoshi、Lee‐Okada Hyeon‐Cheol、Arai Kumiko、Uchiyama Akira、Yamashina Shunhei、Yokomizo Takehiko、Ikejima Kenichi
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: In press Issue: 8 Pages: 1437-1448
  • DOI: 10.1111/jgh.15006
  • Peer Reviewed
• [Journal Article] Role of the high-affinity leukotriene B4 receptor signaling in fibrosis after unilateral ureteral obstruction in mice (2019)
  • Author(s): Kamata Mariko、Amano Hideki、Ito Yoshiya、Fujita Tomoe、Otaka Fumisato、Hosono Kanako、Kamata Kouju、Takeuchi Yasuo、Yokomizo Takehiko、Shimizu Takao、Majima Masataka
  • Journal Title: PLOS ONE Volume: 14 Issue: 2 Pages: 202842-202842
  • DOI: 10.1371/journal.pone.0202842
  • Peer Reviewed / Open Access
• [Journal Article] Papaverine identified as an inhibitor of high mobility group box 1/receptor for advanced glycation end-products interaction suppresses high mobility group box 1-mediated inflammatory responses. (2019)
  • Author(s): Tamada K, Nakajima S, Ogawa N, Inada M, Shibasaki H, Sato A, Takasawa R, Yoshimori A, Suzuki Y, Watanabe N, Oyama T, Abe H, Inoue S, Abe T, Yokomizo T, Tanuma S.
  • Journal Title: Biochem Biophys Res Commun Volume: 511 Issue: 3 Pages: 665-670
  • DOI: 10.1016/j.bbrc.2019.01.136
  • Peer Reviewed / Open Access
• [Journal Article] Cyclooxygenase inhibition in mice heightens adaptive‐ and innate‐type responses against inhaled protease allergen and IL ‐33 (2019)
  • Author(s): Maruyama Natsuko、Takai Toshiro、Kamijo Seiji、Suchiva Punyada、Ohba Mai、Takeshige Tomohito、Suzuki Mayu、Hara Mutsuko、Matsuno Kei、Harada Sonoko、Harada Norihiro、Nakae Susumu、Sudo Katsuko、Okuno Toshiaki、Yokomizo Takehiko、Ogawa Hideoki、Okumura Ko、Ikeda Shigaku
  • Journal Title: Allergy Volume: 印刷中 Issue: 11 Pages: 2237-2240
  • DOI: 10.1111/all.13831
  • Peer Reviewed / Open Access
• [Journal Article] BLT1 Mediates Commensal Bacteria-Dependent Innate Immune Signals to Enhance Antigen-Specific Intestinal IgA Responses (2019)
  • Author(s): Nagatake T, Hirata SI, Koga T, Kuroda E, Kobari S, Suzuki H, Hosomi K, Matsumoto N, Yanrismet Y, Shimojou M, Morimoto S, Sasaki F, Ishii KJ, Yokomizo T, Kunisawa J.
  • Journal Title: Mucosal Immunol . Volume: 12 Issue: 5 Pages: 1082-1082
  • DOI: 10.1038/s41385-019-0175-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An Alternative Pathway to Leukotriene B4 Enantiomers Involving a 1,8-Diol-Forming Reaction of an Algal Oxylipin. (2019)
  • Author(s): Jagusch H., Werner M., Okuno T., Yokomizo T., Werz O., Pohnert G.
  • Journal Title: Org Lett Volume: 21 Issue: 12 Pages: 4667-4670
  • DOI: 10.1021/acs.orglett.9b01554
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dietary supplementation of omega-3 fatty acid eicosapentaenoic acid does not ameliorate pruritus in murine models of atopic dermatitis and psoriasis. (2019)
  • Author(s): Lee H. C., Tominaga M., Yasukawa K., Ohba M., Takahashi N., Honda K., Okuno T., Takamori K., Yokomizo T.
  • Journal Title: J Dermatol Sci Volume: 95 Issue: 3 Pages: 130-133
  • DOI: 10.1016/j.jdermsci.2019.07.010
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• [Journal Article] The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain-Fas-associated death domain interaction. (2019)
  • Author(s): Koutsogiannaki S., Hou L., Babazada H., Okuno T., Blazon-Brown N., Soriano S. G., Yokomizo T., Yuki K.
  • Journal Title: FASEB J Volume: 33 Issue: 11 Pages: 12668-12679
  • DOI: 10.1096/fj.201901360r
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• [Journal Article] Volatile anesthetics isoflurane and sevoflurane directly target and attenuate Toll-like receptor 4 system. (2019)
  • Author(s): Okuno T., Koutsogiannaki S., Hou L., Bu W., Ohto U., Eckenhoff R. G., Yokomizo T., Yuki K.
  • Journal Title: FASEB J Volume: 33 Issue: 12 Pages: 14528-14541
  • DOI: 10.1096/fj.201901570r
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• [Journal Article] Loss of autophagy impairs physiological steatosis by accumulation of NCoR1. (2019)
  • Author(s): Takahashi SS, Sou YS, Saito T, Kuma A, Yabe T, Sugiura Y, Lee HC, Suematsu M, Yokomizo T, Koike M, Terai S, Mizushima N, Waguri S, Komatsu M.
  • Journal Title: Life Sci Alliance. Volume: 3 Issue: 1 Pages: 201900513-201900513
  • DOI: 10.26508/lsa.201900513
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• [Journal Article] Sensitization of Gastric Cancer Cells to Irinotecan by p53 Activation. (2019)
  • Author(s): Zhang, S Kohira, Y Oerita, S Ishimine, M Kobayashi, T Chua, S M B Nakaoka, H Inoue, I Hino, O Yokomizo, T Fukunaga, T H.C., L-O
  • Journal Title: BPB Rep Volume: 2 Pages: 130-133
  • NAID: 130007940492
  • Peer Reviewed / Open Access
• [Journal Article] ロイコトリエンB4第1受容体は滲出型加齢黄斑変性症の新規治療標的となる (2019)
  • Author(s): 佐々木文之、横溝岳彦
  • Journal Title: 実験医学 Volume: 37 Pages: 411-414
• [Journal Article] Transcriptome profiling of refractory atopic keratoconjunctivitis by RNA sequencing (2019)
  • Author(s): Matsuda Akira、Asada Yosuke、Suita Naomasa、Iwamoto Satoshi、Hirakata Toshiaki、Yokoi Norihiko、Ohkawa Yasuyuki、Okada Yukinori、Yokomizo Takehiko、Ebihara Nobuyuki
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 143 Issue: 4 Pages: 1610-1614
  • DOI: 10.1016/j.jaci.2018.11.007
  • Peer Reviewed / Open Access
• [Journal Article] Dietary omega-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses. (2019)
  • Author(s): Hirakata T., Lee H. C., Ohba M., Saeki K., Okuno T., Murakami A., Matsuda A., Yokomizo T.
  • Journal Title: FASEB J Volume: 33 Issue: 3 Pages: 3392-3403
  • DOI: 10.1096/fj.201801805r
  • Peer Reviewed / Open Access
• [Journal Article] Na+-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1 (2018)
  • Author(s): Hori Tetsuya、Okuno Toshiaki、Hirata Kunio、Yamashita Keitaro、Kawano Yoshiaki、Yamamoto Masaki、Hato Masakatsu、Nakamura Motonao、Shimizu Takao、Yokomizo Takehiko、Miyano Masashi、Yokoyama Shigeyuki
  • Journal Title: Nature Chemical Biology Volume: 14 Issue: 3 Pages: 262-269
  • DOI: 10.1038/nchembio.2547
  • Peer Reviewed / Open Access
• [Journal Article] The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in Human Colorectal Cancer (2018)
  • Author(s): Ishimine M, Lee HC, Nakaoka H, Orita H, Kobayashi T, Mizuguchi K, Endo M, Inoue I, Sato K, Yokomizo T
  • Journal Title: Disease Markers Volume: － Pages: 1-7
  • DOI: 10.1155/2018/5280736
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endurance exercise training and high-fat diet differentially affect composition of diacylglycerol molecular species in rat skeletal muscle (2018)
  • Author(s): Kawanishi Noriaki、Takagi Kana、Lee Hyeon-Cheol、Nakano Daiki、Okuno Toshiaki、Yokomizo Takehiko、Machida Shuichi
  • Journal Title: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Volume: 印刷中 Issue: 6 Pages: R892-R901
  • DOI: 10.1152/ajpregu.00371.2017
  • Peer Reviewed / Open Access
• [Journal Article] Applications of mass spectrometry-based targeted and non-targeted lipidomics (2018)
  • Author(s): Lee Hyeon-Cheol、Yokomizo Takehiko
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 504 Issue: 3 Pages: 576-581
  • DOI: 10.1016/j.bbrc.2018.03.081
  • Peer Reviewed / Open Access
• [Journal Article] Leukotriene B4 receptor 2 regulates the proliferation migration and barrier integrity of bronchial epithelial cells (2018)
  • Author(s): M Liu J Shen H Yuan F Chen H Song H Qin Y Li J Xu Q Ye S Li K Saeki T Yokomizo
  • Journal Title: J Cell Physiol Volume: 印刷中 Issue: 8 Pages: 6117-6124
  • DOI: 10.1002/jcp.26455
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stepwise phosphorylation of leukotriene B4 receptor 1 defines cellular responses to leukotriene B4. (2018)
  • Author(s): Nakanishi,Y., Tan,M., Ichiki,T., Inoue,A. Yoshihara,J., Maekawa,N., Takenoshita.I., Yanagida,K., Yamahira,S., Yamaguchi,S., Aoki,J. Nagamune,T., Yokomizo,T., Shimizu,T., and Nakamura,M
  • Journal Title: Science Signaling Volume: 11 (544) Issue: 544 Pages: 5390-5390
  • DOI: 10.1126/scisignal.aao5390
  • Peer Reviewed / Open Access
• [Journal Article] Profiling of bioactive lipids in different dendritic cell subsets using an improved multiplex quantitative LC-MS/MS method. (2018)
  • Author(s): Ohba M., Saeki K., Koga T., Okuno T., Kobayashi Y., Yokomizo T.
  • Journal Title: Biochem Biophys Res Commun Volume: 504 Issue: 3 Pages: 562-568
  • DOI: 10.1016/j.bbrc.2018.06.026
  • Peer Reviewed / Open Access
• [Journal Article] Altered eicosanoid production and phospholipid remodeling during cell culture (2018)
  • Author(s): Okuno Toshiaki、Gij?n Miguel A.、Zarini Simona、Martin Sarah A.、Barkley Robert M.、Johnson Christopher A.、Ohba Mai、Yokomizo Takehiko、Murphy Robert C.
  • Journal Title: Journal of Lipid Research Volume: 59 Issue: 3 Pages: 542-549
  • DOI: 10.1194/jlr.m083030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biological functions of 12(S)-hydroxyheptadecatrienoic acid as a ligand of leukotriene B4 receptor 2. (2018)
  • Author(s): Okuno T., Yokomizo T.
  • Journal Title: Inflamm Regen Volume: 38 Issue: 1 Pages: 29-29
  • DOI: 10.1186/s41232-018-0087-4
  • Peer Reviewed / Open Access
• [Journal Article] Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models. (2018)
  • Author(s): Sasaki F., Koga T., Ohba M., Saeki K., Okuno T., Ishikawa K., Nakama T., Nakao S., Yoshida S., Ishibashi T., Ahmadieh H., Kanavi M. R., Hafezi-Moghadam A., Penninger J. M., Sonoda K. H., Yokomizo T.
  • Journal Title: JCI Insight Volume: 3 Issue: 18 Pages: 96902-96902
  • DOI: 10.1172/jci.insight.96902
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Leukotriene receptors and experience as potential therapeutic targets. (2018)
  • Author(s): Yokomizo,T., Nakamura,M., and Shimizu,T
  • Journal Title: J.Clinical Investigation Volume: 128 Issue: 7 Pages: 2691-2701
  • DOI: 10.1172/jci97946
  • Peer Reviewed / Open Access
• [Presentation] リゾホスファチジルコリンアシル転移酵素1欠損による視覚機能異常 (2020)
  • Author(s): 長田克之, 菱川大介, 相良洋, 岳彦 横., 渡辺すみ子, 進藤英雄, 清水孝雄
  • Organizer: 第62回日本脂質生化学会
• [Presentation] ロイコトリエンB4-BLT1軸は抗糸球体基底膜腎炎モデルの病態促進に寄与する (2020)
  • Author(s): 塩田遼太郎, 城愛理, 横溝岳彦, 鈴木祐介
  • Organizer: 第62回日本脂質生化学会
• [Presentation] Aging causes lipid metabolism imbalance and exacerbates steatohepatitis in high-fat diet-fed mice. (2020)
  • Author(s): Kon, K., Ishizuka, K., Lee-Okada, H. C., Arai, K., Uchiyama, A., Fukada, H., Yamashita, S., Yokomiz, T.,Ikejima, K.
  • Organizer: The International Liver Congress 2020
  • Int'l Joint Research
• [Presentation] ロイコトリエンB4受容体BLT1、BLT2のリガンド認識機構 (シンポジウム) (2020)
  • Author(s): 奥野利明, 横溝岳彦
  • Organizer: 第93回日本生化学会
  • Invited
• [Presentation] 高度不飽和脂肪酸のステロイドホルモン産生における機能解明 (2020)
  • Author(s): 李慶賢, 李賢哲, 横溝岳彦
  • Organizer: 第93回日本生化学会
• [Presentation] 高度不飽和脂肪酸の合成系と局所における役割 (シンポジウム) (2020)
  • Author(s): 李賢哲, 李慶賢, 佐伯和子, 横溝岳彦
  • Organizer: 第93回日本生化学会
  • Invited
• [Presentation] 食餌誘導性肥満におけるロイコトリエンA4水解酵素の役割 (2020)
  • Author(s): 鵜澤博嗣, 佐伯和子, 古賀友紹, 綿田裕孝, 横溝岳彦
  • Organizer: 第93回日本生化学会
• [Presentation] Dietary omega-3 fatty acids alter the lipid mediator profile and the fatty acid composition of membrane phospholipids but was not enough to improve renal insufficiency. (2020)
  • Author(s): Shioda, R., Airi, J.-W., Yokomizo, T., Suzuki., Y.
  • Organizer: American Society of Nephrology(ASN) Kidney Week 2020
  • Int'l Joint Research
• [Presentation] The roles of omega-3 and omega-6 fatty acids in ocular diseases (2019)
  • Author(s): Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids, Invited lecture
  • Int'l Joint Research / Invited
• [Presentation] COX-2, cPGES, and SLCO2A1-dependent ammonic PGE2 accumulation during human labor (2019)
  • Author(s): Okuno, T Takahashi, N Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] Lysophosphatidic Acid Mediates Acute Inflammatory Pain in Mice Models (2019)
  • Author(s): Hashimoto, Y Ito, N Saigusa, D Okuno, T Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] The role of leukotriene A4 hydrolase in metabolism (2019)
  • Author(s): Uzawa, H Saeki, K Koga, T Okuno, T Miyatsuka, T Watada, H Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] β2 integrins affect eicosanoid production and breast cancer growth (2019)
  • Author(s): Koutsogiannaki, S Wang, W Bautista, J Okuno, T Yokomizo, T Yuki, K
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] BLT1 promotes intestinal IgA production against oral vaccine by mediating commensal bacteria-dependent innate immune signals for plasma cell proliferation (2019)
  • Author(s): Nagatake, T Hirata, S I Koga, T Kuroda, E Kobari, S Suzuki, H Hosomi, K Matsumoto, N Yanrismet, Y Shimojou, M Marimoto, S Sasaki, F Ishii, K J Yokomizo, T Kunisawa, J
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] Protective roles of leukotriene B4 receptor type 2 in pneumolysin-induced epithelial injury (2019)
  • Author(s): Chi, Y Saeki, K Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] Spatiotemporal regulation of novel DC subsets by LTB4-BLT1 signaling (2019)
  • Author(s): Koga, T Sasaki, F Saeki, K Okuno, T Nakao, M Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] Deficiency of BLT1, the high-affinity receptor for LTB4, alleviates allergic conjunctivitis in mice (2019)
  • Author(s): Hirakata, T Lee, C H Yasukawa, K Adachi, K Saeki, K Okuno, T Murakami, A Matsuda, A Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] Regulatory mechanism of expression of polyunsaturated fatty acids-related genes (2019)
  • Author(s): Ri, K Lee, C H Yokomizo, T
  • Organizer: 60th ICBL, International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] 高度不飽和脂肪酸欠乏時における脂質関連遺伝子発現の変動 (2019)
  • Author(s): 李賢哲、李慶賢、平形寿彬、横溝岳彦
  • Organizer: 第61回日本脂質生化学会
• [Presentation] 高度不飽和脂肪酸欠乏時における脂質関連遺伝子発現の変動 (2019)
  • Author(s): 李慶賢、李賢哲、横溝岳彦
  • Organizer: 第61回日本脂質生化学会
• [Presentation] ヒト陣痛における羊水中PGE2蓄積は細胞質型PGE合成酵素依存的である (2019)
  • Author(s): 奥野利明、高橋七瀬、横溝岳彦
  • Organizer: 第61回日本脂質生化学会
• [Presentation] リン脂質におけるイオンモビリティ値である衝突断面積の解析 (2019)
  • Author(s): 上野紀子、中西広樹、李賢哲、横溝岳彦
  • Organizer: 第61回日本脂質生化学会
• [Presentation] ロイコトリエンB4産生経路およびロイコトリエンB4受容体BLT1は滲出型加齢黄斑変性症の新規治療標的となる (2019)
  • Author(s): 佐々木文之、古賀友紹、横溝岳彦
  • Organizer: 第40回日本炎症・再生学会 (シンポジウム)
  • Invited
• [Presentation] 代謝におけるロイコトリエンA4水解酵素の役割の解析 (2019)
  • Author(s): 鵜澤博嗣、古賀友紹、佐伯和子、奥野利明、綿田裕孝、横溝岳彦
  • Organizer: 第92回日本生化学会
• [Presentation] セリン加水分解酵素ABHD4の生化学的解析および機能解析 (2019)
  • Author(s): 李賢哲、Cravatt, B F、横溝岳彦
  • Organizer: 第92回日本生化学会
• [Presentation] Lysophosphatidic acid mediates formalin-induced inflammatory pain in mice (2019)
  • Author(s): Hoshino, Y Ito, N Saigusa, D Okuno, T Yokomizo, T
  • Organizer: 49th Annual meeting of the society for Neuroscience
  • Int'l Joint Research
• [Presentation] The roles of leukotriene B4 receptor in macrophage and dendritic cell (2019)
  • Author(s): Yokomizo, T
  • Organizer: 16th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, Symposium
  • Int'l Joint Research / Invited
• [Presentation] Identification of a novel mutation in SLCO2A1 gene, encoding a prostaglandin transporter (2019)
  • Author(s): Okuno, T Jimbo, K Ohgaki, R Kanai, Y Shimizu, T Yokomizo, T
  • Organizer: 16th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, Symposium
  • Int'l Joint Research
• [Presentation] The effects of dietary supplementation of an omega-3 fatty acid eicosapentaenoic acid on pruritus in murine atopic dermatitis and psoriasis models (2019)
  • Author(s): Yasukawa, K Lee, C H Tominaga, M Ohba, M Takahashi, N Honda, K Okuno, T Takamori, K Yokomizo, T
  • Organizer: 16th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Int'l Joint Research
• [Presentation] Age-related enhancement of cellular stresses and lipotoxicity exacerbates dietary steatohepatitis in mice (2019)
  • Author(s): Ishizuka, K Kon, K Lee, H C Arai, K Uchiyama, A Fukada, H Yamashina, S Yokomizo, T Ikejima, A Ikejima, K
  • Organizer: AASLD The Liver Meeting 2019
  • Int'l Joint Research
• [Presentation] Dietary glycine prevents metabolic steatohepatitis in diabetic KK-Ay mice through remodeling of hepatic lipid (2019)
  • Author(s): Tada, M Uchiyama, A Lee, H C Arai, K Fukuhara, K Kon, K Yamashina, S Ikejima, K
  • Organizer: AASLD The Liver Meeting 2019
  • Int'l Joint Research
• [Presentation] The role of leukotriene A4 hydrolase in metabolism (2019)
  • Author(s): H Uzawa T Yokomizo
  • Organizer: Keystone Symposium Obesity and Adipose Tissue Biology
  • Int'l Joint Research
• [Presentation] The roles of leukotriene B4 receptor in macrophage and dendritic cell (2019)
  • Author(s): T Yokomizo
  • Organizer: The kick-off symposium of advanced graduate program for future medicine and health care
  • Int'l Joint Research / Invited
• [Presentation] Leukotriene B4 promotes neovascularization and macrophage recruitment in age-related macular degeneration (AMD) (2019)
  • Author(s): T Yokomizo F Sasaki
  • Organizer: Keystone Symposium Lipidomics and Functional Metabolic Pathways in Disease
• [Presentation] Dietary omega-3 fatty acids alleviate allergic conjunctivitis in a mouse model (2018)
  • Author(s): T Hirakata C H Lee M Ohba T Okuno A Murakami A Matsuda T Yokomizo
  • Organizer: ARVO 2018
  • Int'l Joint Research
• [Presentation] Control of mouse allergic conjunctivitis by resolvins (2018)
  • Author(s): S Iwamoto T Yokomizo A Murakami A Matsuda
  • Organizer: ARVO 2018
  • Int'l Joint Research
• [Presentation] An algal precursor rearranges in a new 1 8-diol forming reaction to bioactive LTB4 enantiomers (2018)
  • Author(s): H Jagusch M Werner T Okuno T Yokomizo O Watz G Pohnert
  • Organizer: European Lipid Meeting 2018
  • Int'l Joint Research
• [Presentation] Leukotriene B4 receptor type 2 protects against CysLT1 signaling-related acute lung injury (2018)
  • Author(s): A Jo-Watanabe M Shigematsu K Saeki T Koga M Ohba T Okuno T Yokomizo
  • Organizer: Keystone Symposium
  • Int'l Joint Research
• [Presentation] Phospholipid remodeling altered eicosanoid production during cell culture (2018)
  • Author(s): T Okuno +M A Gijon T Yokomizo R C Murphy
  • Organizer: European Lipid Meeting 2018 GPCR Structure and Function
  • Int'l Joint Research
• [Presentation] Crystal structure of leukotriene B4 receptor 1 bound with an inverse agonist (2018)
  • Author(s): T Okuno T Hori S Yokoyama T Yokomizo
  • Organizer: International GPCR symposium
  • Int'l Joint Research
• [Presentation] 12-hydroxyheptadecatrienoic acid accelerates epithelial wound healing through leukotriene B4 receptor 2 (2018)
  • Author(s): T Yokomizo
  • Organizer: Keystone Symposium the resolution of inflammation in health and disease
  • Int'l Joint Research
• [Presentation] BLT1 and BLT2 two GPCRs for lipid mediators (2018)
  • Author(s): T Yokomizo
  • Organizer: International GPCR symposium
  • Int'l Joint Research / Invited
• [Presentation] A fatty acid 12-hydroxyheptadecatrienoic acid accelerates corneal wound healing through leukotriene B4 receptor 2 (2018)
  • Author(s): T Yokomizo S Iwamoto T Koga M Ohba T Okuno M Koike A Murakami A Matsuda
  • Organizer: Keystone Symposium GPCR Structure and Function
  • Int'l Joint Research
• [Presentation] 生理活性脂質12-HHTのBLT2受容体を介した生体保護的役割 (2018)
  • Author(s): 佐伯和子 重松美沙子 古賀友紹 奥野利明 横溝岳彦
  • Organizer: 第91回日本生化学会 シンポジウム
  • Invited
• [Presentation] アレルギー性結膜炎におけるオメガ3脂肪酸の効果の検証 (2018)
  • Author(s): 平形寿彬 李賢哲 大塲麻衣 佐伯和子 奥野利明 松田彰 村上晶 横溝岳彦
  • Organizer: 第60回日本脂質生化学会
• [Presentation] マウスアレルギー性結膜炎モデルにおけるオメガ３脂肪酸食効果の検証 (2018)
  • Author(s): 平形寿彬 李賢哲 大塲麻衣 佐伯和子 奥野利明 松田彰 村上晶 横溝岳彦
  • Organizer: 第1回日本眼科アレルギー学会学術集会
• [Presentation] 薬物代謝酵素カルボキシルエステラーゼの消化器癌における発現調節機構の解明 (2018)
  • Author(s): 折田創 伊志嶺百々子 李賢喆 小泉明博 村井勇太 加藤永記 山本陸 上田脩平 櫻庭駿介 徳田智史 朝倉孝延 氷室貴規 櫛田知志 櫻田睦 田中顕一郎 前川博 横溝岳彦 佐藤浩一
  • Organizer: 第56回日本癌治療学会学術集会
• [Presentation] 生理活性脂質受容体研究への質量分析計の応用 (2018)
  • Author(s): 横溝岳彦
  • Organizer: 第31回Future of Radiology
  • Invited
• [Presentation] ロイコトリエンB4受容体に関する最近の知見 (2018)
  • Author(s): 横溝岳彦
  • Organizer: Kobe Biological Science Forum
  • Invited
• [Presentation] 生理活性脂質受容体の機能解析：ゼロから創薬への挑戦 (2018)
  • Author(s): 横溝岳彦
  • Organizer: New Insight Crosstalk Meeting 2018
  • Invited
• [Presentation] ロイコトリエンB4受容体BLT1発現が規定する単球・樹状細胞サブセット (2018)
  • Author(s): 横溝岳彦
  • Organizer: 第28回日本樹状細胞研究会 特別講演
  • Invited
• [Presentation] 生理活性脂質と受容体 (2018)
  • Author(s): 横溝岳彦
  • Organizer: 第4回川島カンファレンス
  • Invited
• [Presentation] ロイコトリエンA4水解酵素の代謝における役割の解析 (2018)
  • Author(s): 鵜澤博嗣 古賀友紹 佐伯和子 宮塚健 綿田裕孝 横溝岳彦
  • Organizer: 第91回日本生化学会
• [Presentation] ロイコトリエンA4水解酵素の代謝における解析 (2018)
  • Author(s): 鵜澤博嗣 古賀友紹 奥野利明 佐伯和子 横溝岳彦
  • Organizer: 第60回日本脂質生化学会
• [Book] マークス臨床生化学 (2020)
  • Author(s): 横溝 岳彦 訳
  • Total Pages: 654
  • Publisher: 医学書院
  • ISBN: 9784260041393
• [Remarks] 順天堂大学医学部生化学第一講座
  • URL: http://plaza.umin.ac.jp/j_bio/
• [Remarks] 順天堂大学生化学第一講座のホームページ
  • URL: http://plaza.umin.ac.jp/j_bio/
• [Remarks] 順天堂大学生化学第一講座
  • URL: http://plaza.umin.ac.jp/j_bio/index.html
• [Remarks] 加齢黄斑変性症の病的血管新生のメカニズムを解明～ 加齢黄斑変性症の新規治療法への道筋 ～
  • URL: https://www.juntendo.ac.jp/news/20180920-01.html
• [Remarks] オメガ３脂肪酸のアレルギー性結膜炎への改善効果を発見～ 亜麻仁油が花粉症患者を救う？ ～
  • URL: https://www.juntendo.ac.jp/news/20181105-04.html
• [Patent(Industrial Property Rights)] PREVENTIVE OR THERAPEUTIC AGENT FOR AGE-RELATED MACULAR DEGENERATION (2018)
  • Inventor(s): Sasaki F, Yokomizo T
  • Industrial Property Rights Holder: Sasaki F, Yokomizo T
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Overseas