Basic scientific research for formulating drugs for treatment of hypertension

• Project/Area Number: 24590337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kinki University
• Principal Investigator: TAKAHASHI Hideo 近畿大学, 医学部, 教授 (60335627)
• Co-Investigator(Kenkyū-buntansha): NIWA Atsuko 近畿大学, 医学部, 講師 (60122082) ; NISHIBORI Masahiro 岡山大学, 医歯薬総合研究科, 教授 (50135943) ; RYU Katsuyaku 岡山大学, 医歯薬総合研究科, 助教 (40432637) ; 中村 恭子 近畿大学, 付置研究所, 助教 (10512197) ; 大島 佳奈 近畿大学, 医学部, 助手 (60278653)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: High mobility group box1 / SHR / 高血圧症 / 抗HMGB1抗体 / high mobility group box1

Outline of Final Research Achievements

Recent studies have shown that high mobility group box1 (HMGB1) plays roles in immune response. We have reported that anti-HMGB1 Ab inhibited the progression of brain infarction and atherosclerosis. However, little is known whether HMGB1 induces the vascular injury, we investigated the involvement of HMGB1 in the endothelial dysfunction and injury using stroke-prone spontaneously hypertensive rats (SHRSP). It is well known that the endothelial dysfunction and injury induces hypertension. Although we could not prove the effect of HMGB1 on the endothelial dysfunction and injury, during this project, we found the mechanism of neutrophil-induced endothelial dysfunction and injury. Moreover, we found a mediator which inhibited the activation of neutrophil. Therefore, we continue the promotion of basic scientific research for formulating drugs for treatment of hypertension.

Research Products

• [Journal Article] Glycyrrhizin inhibits traumatic brain injury by reducing HMGB1-RAGE interaction. (2014)
  • Author(s): Okuma Y, Liu K, Wake H, Liu R, Nishimura Y, Hui Z, Teshigawara K, Haruma J, Yamamoto Y, Yamamoto H, Date I, Takahashi HK, Mori S, Nishibori M.
  • Journal Title: Neuropharmacology Volume: 85 Pages: 18-26
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of Moesin in the Development of Morphine Analgesic Tolerance through P-glycoprotein at the Blood–Brain Barrier (2014)
  • Author(s): Kobori T, Fujiwara S, Miyagi K, Harada S, Nakamoto K, Nakagawa T, Takahashi H, Narita M, Tokuyama S.
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 29 Issue: 6 Pages: 482-489
  • DOI: 10.2133/dmpk.DMPK-14-RG-042
  • NAID: 130004933556
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes (2013)
  • Author(s): Takahashi H、Sadamori H、Teshigawara K、Niwa A、Liu K、Wake H、Mori S、Yoshino T、Nishibori M
  • Journal Title: Eur J Phamacol Volume: Vol.718、No.1-3 Issue: 1-3 Pages: 305-313
  • DOI: 10.1016/j.ejphar.2013.08.017
  • Peer Reviewed
• [Journal Article] Role of cell-cell interactions in high mobility group box 1 cytokine activity in human peripheral blood mononuclear cells and mouse splenocytes (2013)
  • Author(s): Takahashi HK,Sadamori H, Liu K, Wake H, Mori S, Yoshino T, Yamamoto Y, Yamamoto H,Nishibori M.
  • Journal Title: Eur J Pharmacol Volume: 701 Pages: 194-202
  • Peer Reviewed
• [Journal Article] Anti-high mobility group box-1 antibody therapy for traumatic brain injury (2012)
  • Author(s): Okuma Y, Liu K, Wake H, Zhang J, Maruo T, Date I, Yoshino T, Ohtsuka A, Otani N, Tomura S, Shima K, Yamamoto Y, Yamamoto H, Takahashi H K, Mori S, Nishibori M
  • Journal Title: Annals of Neurology Volume: 72 Issue: 3 Pages: 373-384
  • DOI: 10.1002/ana.23602
  • NAID: 130004427993
  • Peer Reviewed
• [Journal Article] Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain (2012)
  • Author(s): Shichita T
  • Journal Title: Nature Medicine Volume: 18 Issue: 6 Pages: 911-917
  • DOI: 10.1038/nm.2749
  • Peer Reviewed
• [Presentation] Voluntary exercise induces neurogenesis in hypothalumus and improves homeostatic functions after stroke (2015)
  • Author(s): 丹羽 淳子、赤星 保光、堀内 喜高、濱崎 真一、小堀 宅郎、西堀 正洋、高橋 英夫
  • Organizer: 第88回日本薬理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] IL-18 promotes macrophage M2 polarization (2015)
  • Author(s): 小堀 宅郎、濱崎 真一、丹羽 淳子、高橋 英夫
  • Organizer: 第88回日本薬理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] HMGB1 によるヒスタミン誘導性免疫応答調節効果 (2014)
  • Author(s): 濱﨑真一、丹羽淳子、小堀宅郎、西堀正洋、髙橋英夫
  • Organizer: 第125回日本薬理学会近畿部会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2014-06-20
• [Presentation] 自発運動は脳卒中後の視床下部神経再生を促進する (2014)
  • Author(s): 丹羽淳子、赤星保光、堀内喜高、濱﨑真一、小堀宅郎、西堀正洋、 髙橋英夫
  • Organizer: 第125回日本薬理学会近畿部会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2014-06-20
• [Presentation] ホメオスタシス機構と創薬
  • Author(s): 髙橋 英夫
  • Organizer: 第34回癌免疫外科研究会
  • Place of Presentation: 岡山市
  • Invited
• [Presentation] The inhibitory effect of histamine on high mobility group box 1 activity via the cAMP/PKA pathway.ヒスタミンH2受容体刺激によるHMGB1誘導性免疫応答調節効果の基礎的検討
  • Author(s): 濱崎 真一、丹羽 淳子、上野 浩司、西堀 正洋、髙橋 英夫
  • Organizer: 第87回日本薬理学会
  • Place of Presentation: 仙台市
• [Presentation] Voluntary exercise enhances neurogenesis in hypothalamus after stroke.自発運動は脳卒中後の視床下部神経再生を促進する
  • Author(s): 丹羽 淳子、赤星 保光、堀内 喜高、濱﨑 真一、西堀 正洋、髙橋 英夫
  • Organizer: 第87回日本薬理学会
  • Place of Presentation: 仙台市
• [Presentation] ステロイド療法と作用機序
  • Author(s): 髙橋 英夫
  • Organizer: 第62回日本アレルギー学会秋季学術大会 シンポジウム7 アレルギー疾患におけるステロイド療法の理論と実際
  • Place of Presentation: 国際会議場（大阪府）
  • Invited
• [Book] Annaual Review 呼吸器 2014 (2014)
  • Author(s): 髙橋英夫
  • Total Pages: 273
  • Publisher: 中外医学社
• [Remarks] 近畿大学医学部薬理学教室
  • URL: http://www.med.kindai.ac.jp/pharma/
• [Patent(Industrial Property Rights)] 好中球活性化に起因する疾患の治療薬、治療方法及び検査方法 (2013)
  • Inventor(s): 西堀正洋
  • Industrial Property Rights Holder: 西堀正洋
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-05-28
• [Patent(Industrial Property Rights)] 好中球活性化調節剤 (2012)
  • Inventor(s): 西堀正洋,森秀治,和氣秀徳,髙橋英夫,劉克約,勅使河原匡
  • Industrial Property Rights Holder: 西堀正洋,森秀治,和氣秀徳,髙橋英夫,劉克約,勅使河原匡
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-129232
  • Filing Date: 2012-06-06