Immunosuppressive effect of novel physical medicine and identification of its receptor

• Project/Area Number: 15K12514
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Kumamoto University
• Principal Investigator: Kai Hirofumi 熊本大学, 大学院生命科学研究部(薬), 教授 (30194658)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 物理療法 / アルツハイマー病 / 免疫制御 / 免疫抑制

Outline of Final Research Achievements

Our laboratory has comprehensively studied the biological effects of mild electrical stimulation (MES, 0.1-ms pulse width, 55-pps) with heat shock (HS, 42℃). Specifically, MES+HS improved the inflammatory symptom in mouse models of diabetes and chronic kidney disease. To determine whether MES+HS suppresses psoriasis pathology, I used imiquimod-induced psoriasis mouse model. Notably, MES+HS (10 min, daily) significantly suppressed imiquimod-induced psoriasis-like skin hyperplasia, activation of Akt and expression of psoriasis-related genes (Krt6a, IL-17A and IL-22). Taken together, MES+HS improves psoriasis, at least in part, by suppressing the expression of cytokines．

Research Products

• [Journal Article] Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm. (2017)
  • Author(s): Koga T, Shiraki N, Yano S, Suico MA, Morino-Koga S, Sato T, Shuto T, Kume S, Kai H
  • Journal Title: BMC Biotechnology Volume: 17 Issue: 1 Pages: 14-14
  • DOI: 10.1186/s12896-017-0331-z
  • Peer Reviewed / Open Access
• [Journal Article] cAMP-dependent protein kinase A acts as a negative regulator for nontypeable Haemophilus influenzae-induced GM-CSF expression via inhibition of MEK-ERK signaling pathway. (2016)
  • Author(s): Tasaki Y, Wang WY, Konduru AS, Komatsu K, Matsuyama S, Kai H, Li JD
  • Journal Title: Integr Mol Med. Volume: 3 Issue: 6 Pages: 1-5
  • DOI: 10.15761/imm.1000261
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Activation of heat shock response to treat obese subjects with type 2 diabetes: a prospective, frequency-escalating, randomized, open-label, triple-arm trial. (2016)
  • Author(s): Kondo T, Goto R, Ono K, Kitano S, Suico MA, Sato M, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E.
  • Journal Title: Sci Rep. Volume: 19 Issue: 1 Pages: 35690-35690
  • DOI: 10.1038/srep35690
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 医療機器と薬学 (2016)
  • Author(s): 甲斐 広文
  • Journal Title: 薬剤学 Volume: 76 Pages: 92-98
  • NAID: 130005264458
  • Peer Reviewed / Open Access
• [Journal Article] 最適化された微弱パルス電流と温熱の併用療法（physical medicine）の基礎と臨床 (2015)
  • Author(s): 甲斐 広文, 近藤 龍也, 荒木 栄一
  • Journal Title: ファルマシア Volume: 51 Pages: 1033-1037
  • NAID: 130007447895
  • Peer Reviewed / Open Access
• [Journal Article] The effect of mild electrical stimulation with heat shock on diabetic KKAy mice. (2015)
  • Author(s): Kai Y, Tsurekawa Y, Fukuda R, Omachi K, Piruzyan M, Okamoto Y, Motomura K, Suico MA, Shuto T, Kondo T, Araki E, Kai H.
  • Journal Title: Integr Mol Med. Volume: 3 Issue: 1 Pages: 473-477
  • DOI: 10.15761/imm.1000190
  • Peer Reviewed / Open Access
• [Journal Article] Podocyte p53 limits the severity of experimental Alport syndrome. (2015)
  • Author(s): Fukuda R., et al.
  • Journal Title: Jounal of American Society of Nephrology Volume: just accepted Issue: 1 Pages: 144-157
  • DOI: 10.1681/asn.2014111109
  • Peer Reviewed / Open Access
• [Presentation] タンパク質フォールディングは遺伝性腎炎アルポート症候群の新たな標的となり得るか (2017)
  • Author(s): 甲斐 広文, 大町 紘平, Mary Ann Suico, 首藤 剛
  • 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）
  • Year and Date: 2017-03-15
  • Invited
• [Presentation] 微弱パルス電流と温熱の同時印加はimiquimod誘導性乾癬モデルにおけるケラチノサイトの過剰増殖を抑制する (2017)
  • Author(s): 連川 雄, 甲斐 友佳理, 中野 義雄, 森田 光咲, 高田 雅文, 森内 将貴, Mariamu Piruzyan, Mary Ann Suico, 首藤 剛, 甲斐 広文
  • 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）
  • Year and Date: 2017-03-15
• [Presentation] タウリンは TRPV1 を阻害し，線虫において酸化ストレス抑制作用を示す (2017)
  • Author(s): 森内 将貴, 中野 義雄, 連川 雄, Mariam Piruzyan, 高田 雅文, 森田 光咲, Niraj Chaudhry, Mary Ann Suico, 首藤 剛, 甲斐 広文
  • 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）
  • Year and Date: 2017-03-15
• [Presentation] 微弱パルス電流及び温熱の同時印加はimiquimod誘導性乾癬モデルにおける表皮の肥厚化を抑制する (2016)
  • Author(s): 連川 雄, 甲斐 友佳理, 中野 義雄, 森田 光咲, 高田 雅文, 森内 将貴, Mariamu Piruzyan, Mary Ann Suico, 首藤 剛, 甲斐 広文
  • Organizer: 第３３回日本薬学会九州支部大会
  • Place of Presentation: 鹿児島大学 郡元キャンパス
  • Year and Date: 2016-12-03
• [Presentation] 遺伝性プロテインミスフォールディング病に対する創薬 (2016)
  • Author(s): 甲斐 広文
  • Organizer: 第３７回日本臨床薬理学会学術総会
  • Place of Presentation: 米子コンベンションセンター
  • Year and Date: 2016-12-01
  • Invited
• [Presentation] Mild electrical stimulation with heat shock suppresses skin hyperplasia in imiquimod-induced psoriasis model. (2016)
  • Author(s): Tsurekawa Y, Kai Y, Morita M, Takada M, Moriuchi M, Okita G, Suico MA, Shuto T, Kai H
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: Merborne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] 最適化された微弱パルス電流と温熱の臨床応用 (2016)
  • Author(s): 甲斐 広文
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜（神奈川）
  • Year and Date: 2016-03-26
  • Invited
• [Presentation] 乾癬における最適化微弱電流の病態改善効果に関する研究 (2016)
  • Author(s): 連川 雄, 森内 将貴, 沖田 剛, 中野 義雄, Mariam Piruzyan, 高田 雅文, 森田 光咲, Mary Ann Suico, 首藤 剛, 甲斐 広文
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜（神奈川）
  • Year and Date: 2016-03-26
• [Presentation] The Effect and Mechanism of Mild Electrical Stimulation on Pro-inflammatory Cytokines in vivo and in vitro (2015)
  • Author(s): Mariam Piruzyan, Ihori Shitanda, Yuichiro Shimauchi, Mary Ann Suico, Tsuyoshi Shuto, Hirofumi Kai
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫）
  • Year and Date: 2015-12-01
• [Presentation] The immunosuppressive effect of mild electrical stimulation via NFAT pathway is a promising therapeutic approach for inflammation (2015)
  • Author(s): Mariam Piruzyan, Ihori Shitanda, Yuichiro Shimauchi, Mary Ann Suico, Tsuyoshi Shuto, Hirofumi Kai
  • Organizer: 第32回日本薬学会九州支部大会
  • Place of Presentation: 九州保健福祉大学（宮崎）
  • Year and Date: 2015-11-28
• [Presentation] The Immunosuppressive Effect of Mild Electrical Stimulation is a Promising Therapy for Inflammation (2015)
  • Author(s): Mariam Piruzyan, Ihori Shitanda, Yuichiro Shimauchi, Mary Ann Suico, Tsuyoshi Shuto, Hirofumi Kai
  • Organizer: 第68回日本薬理学会西南部会
  • Place of Presentation: 海峡メッセ下関（山口）
  • Year and Date: 2015-11-21
• [Presentation] Mild pulse electrical stimulation at high frequency (5500 pps) suppresses brain inflammation related to Alzheimer’s disease. (2015)
  • Author(s): G. Okita, H. Kai
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Presentation] Beneficial effects and the molecular mechanisms of specific mild electrical stress as physical medicine (2015)
  • Author(s): H. Kai, T. Kondo, M.A. Suico, T. Shuto E. Araki
  • Organizer: International Symposium on Chronic Inflammatory Diseases, Kumamoto (ISCIDK2015)
  • Place of Presentation: 熊本大学薬学部（熊本）
  • Year and Date: 2015-10-16
  • Int'l Joint Research / Invited
• [Presentation] The immunosuppressive effect of mild electrical stimulation via NFAT pathway is a promising therapeutic approach for inflammation (2015)
  • Author(s): M. Piruzyan, I. Shitanda, Y. Shimauchi, M. Suico, T. Shuto, H. Kai immunosuppressive effect of mild electrical stimulation via NFAT pathway is a promising therapeutic approach for inflammation
  • Organizer: International Symposium on Chronic Inflammatory Diseases, Kumamoto (ISCIDK2015)
  • Place of Presentation: 熊本大学薬学部（熊本）
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Presentation] Mild electrical stimulation suppresses IL22 mRNA expression in imiquimod-induced psoriasis mouse model (2015)
  • Author(s): Y. Tsurekawa, M. Suico, M. Moriuchi, G. Okita, Y. Nakano, M. Piruzyan, M. Takada, M. Morita, T. Shuto, H. Kai
  • Organizer: International Symposium on Chronic Inflammatory Diseases, Kumamoto (ISCIDK2015)
  • Place of Presentation: 熊本大学薬学部（熊本）
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Remarks] 熊本大学大学院薬学教育部 遺伝子機能応用学研究室
  • URL: http://molmed730.org/index.html
• [Remarks] 熊本大学大学院薬学教育部 遺伝子機能応用学研究室
  • URL: http://molmed730.org/index.html