Dual Modulation of Airway Smooth Muscle Contraction by Th2 Cytokines via Matrix Metalloproteinase-1 Production

• Project/Area Number: 19390065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kumamoto Health Science University
• Principal Investigator: ITO Yusii Kumamoto Health Science University, 大学院, 教授 (80037506)
• Co-Investigator(Kenkyū-buntansha): OIKE Masahiro 九州大学, 大学院 医学研究院, 准教授 (70271103) ; 木村 千稚 九州大学, 医学(系)研究科(研究院), 研究員 (90359935)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Chiwaka
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2007: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
• Keywords: 気道 / 平滑筋 / 気道過敏性 / サイトカイン / IL-13 / IL-4 / Ca^<2+> / ミオシン軽鎖

Research Abstract

研究成果の概要:Th2 サイトカインであるIL-4 及びIL-13 は気道平滑筋の収縮増強効果を有し、この増強効果には細胞内Ca 濃度や収縮蛋白のCa 感受性、MLCK のリン酸化は全く関与しないことを明らかにした。結論としてTh2 サイトカインによる収縮増強効果にはMMP-1 が関与し気道平滑筋細胞と細胞外コラーゲンの網状組織の再構築が関与することを世界に先駆け明らかにした。

Research Products

• [Journal Article] Gastric relaxation induced by electrical and chemical stimulation of the area postrema (2009)
  • Author(s): Kawachi, M., Hori, N., Takei, M., Kurimoto, T., Akaike, N., Ito,Y
  • Journal Title: General Physiology & Biophysics 27 Pages: 243-252
• [Journal Article] Histamine responses of large neostriatal interneurons in histamine H1 and H2 receptor knock-out mice (2009)
  • Author(s): Ogawa, S., Yanai, K., Watanabe, T., Wang, ZM., Akaike, H., Ito, Y., Akaike, N
  • Journal Title: Brain Research Bulletin 78 Pages: 189-194
• [Journal Article] Differential effects of divalent cations on spontaneous ans evoked glycine release from spinal interneurns (2009)
  • Author(s): Maeda, M., Tanaka, E., Shoudai, K., Nonaka, K., Murayama, N., Ito, Y., Akaike, N
  • Journal Title: Journal of Neurophysiology 101 Pages: 1103-1113
• [Journal Article] Gastric relaxation induced by electrical and chemical stimulation of the area postrema (2009)
  • Author(s): Kawachi, M., Hori, N., Takei, M., Kurimoto, T., Akaike, N., Ito, Y
  • Journal Title: General Physiology & Biophysics 27 Pages: 243-252
  • Peer Reviewed
• [Journal Article] Differential effects of divalent cations on spontaneous and evoked glycine release from spinal interneurons. (2009)
  • Author(s): Maeda, M., Tanaka, E., Shoudai, K., Nonaka, K., Ito, Y., Akaike, N.
  • Journal Title: Journal of Neurophysiology 101 Pages: 1103-1113
  • Peer Reviewed
• [Journal Article] responses of large neostriatal interneurons in histamine H1 and H2receptor knock-out mice (2009)
  • Author(s): Ogawa, S., Yanai, K., Watanabe, T., Wang, ZM., Akaike, H., Ito, Y., Akaike, N
  • Journal Title: Brain Research Bulletin 78 Pages: 189-194
  • Peer Reviewed
• [Journal Article] Synergistic Activation of Vascular TRPC6 Channel by Receptor and Mechanical Stimulation via Phospholipase C/Diacylglycerol and Phospholipase A2/{omega}-Hydroxylase/ 20-HETE Pathways. (2009)
  • Author(s): Inoue, R, Jensen, LJ, Jian Z, Shi J, Hai L, Lurie AI, Henriksen FH, Salmonsson M, Morita H, Kawarabayashi Y, Mori M, Mori Y, Ito Y.
  • Journal Title: Circ Res 14 (In press)
  • Peer Reviewed
• [Journal Article] Quantitative analysis of toxin extracts from various tissues of wild and cultured puffer fish by an electrophysiological merhod (2008)
  • Author(s): Sasaki, K., Takayama, Y., Tahara, T., Anraku, K., Ito, Y., Akaike, N
  • Journal Title: Toxicon 51 Pages: 606-614
• [Journal Article] Dual modulation of airway smooth muscle contraction by TH2 cytokines via matrix metalloproteinase-1 production (2008)
  • Author(s): Ohta, Y., Hayashi, M., Kanenura, T., Abe, K., Ito, Y., Oike, M
  • Journal Title: The Journal of Immunology 180 Pages: 4191-4199
• [Journal Article] Holstein-Rathlou, NH., Jensen, Lj The role of L-and T-type calcium channels in local and remote calcium responses in rat mesenteric terminal arterioles (2008)
  • Author(s): Braunstein, TH., Inoue, R., Crebbs, L., Oke, M., Ito, Y
  • Journal Title: Vascular Research 46(2) Pages: 138-151
• [Journal Article] Dual modulation of airway amooth muscle contraction by Th2 cytokines via matrix metalloproteinase-1 production (2008)
  • Author(s): Ohta Y, Hayashi M, Kanemaru T, Abe K, Ito Y, Oike M
  • Journal Title: The Journal of Immunology 180 Pages: 4191-4199
  • Peer Reviewed
• [Journal Article] Quantitative analysis of toxin extracts from various tissues of wild and cultured puffer fish by an electrophysiological method (2008)
  • Author(s): Sasaki, K, Takayama, Y Tahara T, Anraku, K, Ito Y, Akaike N
  • Journal Title: Toxicon 51 Pages: 606-614
  • Peer Reviewed
• [Journal Article] The role of L-and T-type calcium channels in local and remote calcium responses in rat mesenteric terminal arterioles (2008)
  • Author(s): Braunstein, TH., Inoue, R., Crebbs, L., Oke, M., Ito, Y., Holstein-Eathlou, NH., Jensen, Lj
  • Journal Title: Vascular Research 46 (2) Pages: 138-151
  • Peer Reviewed
• [Journal Article] Quantitative analysis of toxin extracts from varlous tissues of wild and cultured puffer fish by an electrophysiological method (2008)
  • Author(s): Sasaki K, Takayama Y, Tahara T, Anraku K, Ito Y, Akaike N
  • Journal Title: Toxicon 51 Pages: 606-614
  • Peer Reviewed
• [Journal Article] Membrane stretch-induced activationb of a TRPM4-like nonselective cation channel in cerebral artery myocytes (2007)
  • Author(s): Morita,H., Honda, A., Inoue, R., Ito, Y., Abe, K., Nelson, MT., Brayden, JE
  • Journal Title: Journal of Pharmacological Sciences 103 Pages: 417-426
• [Journal Article] Membrane stretch-induced activation of a TRPM4-like nonselective Cation channel in cereberal artery myocytes (2007)
  • Author(s): Morita H, Honda A, Inoue R, Ito Y, Abe K, Nelson M, Brayden J
  • Journal Title: Journal of Pharmacological Sciences 103 Pages: 417-426
  • Peer Reviewed
• [Presentation] New aspect of Purinergic Regulation in Cerebral Artery Myocyte (2009)
  • Author(s): Hiromitsu Morita^1, Megumi Sugihara^<1, 2>, Yushi Ito^3, Masato Hirata^2, Kihachiro Abe^1
  • Organizer: International Stroke Conference
  • Place of Presentation: San Diego, CA, USA
• [Presentation] EGF receptor regulates volume-regulated anion channel in squamous cell carcinoma cells of HST-1 and A431 (2009)
  • Author(s): Megumi Sugihara^<1, 2>, Miho Matsuda^2, Ryosuke Inoue^1, Yushi Ito^3, Kihachiro Abe^1, Masato Hirata^2, Hiromitsu Morita^1
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 神奈川県横浜市
• [Presentation] The 8th Congress of the Federation of Asian and Oceania Physiological Societies Pusan Chorea (2009)
  • Author(s): Hironari Akaike, II-Sung Jang, Nobuaki Hori, Satio Ogawa, Norio Akaike, Yushi Ito.
  • Organizer: 第60回日本薬理学会西南部会
  • Place of Presentation: 宮崎県
• [Presentation] 血管平滑筋におけるP2Xヘテロ複合体の機能的発現 (2008)
  • Author(s): 杉原恵美^<1, 2>, 森田浩光^2, 伊東祐之^3, 松田美穂^1, 安部喜八郎^2, 平田雅人^1
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会総会合同大会
  • Place of Presentation: 兵庫県神戸市
• [Presentation] activates P2X receptor and regulate vascular tone in rat arterial smooth muscle (2008)
  • Author(s): Megumi Sugihara^<1, 2>, Miho Matsuda^2, Shunichi Kajioka^3, Masato Hirata^2, Kihachiro Abe^1, Yushi Ito^4, Hiromitsu Morita^1
  • Organizer: Vascular & Smooth Muscle Physiology
  • Place of Presentation: London, UK
• [Presentation] ヒト舌癌由来細胞株HST-1に存在する外向き整流性、低浸透圧・ATP感受性クロライド電流 (2007)
  • Author(s): 杉原 恵美, 森田 浩光, 井上 良介, 松田 美穂, 中野 修治, 井上 隆司, 伊東 祐之, 安部 喜八郎, 平田 雅人
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-16
• [Presentation] Quantitative analysis of toxin extracts from various tissues of wild and cultured puffer fish by an electrophysiological method (2007)
  • Author(s): 佐々木恵太, 高山靖規, 伊東祐之, 赤池紀生
  • Organizer: 第60 回日本薬理学会西南部会
  • Place of Presentation: 宮崎
  • Year and Date: 2007-11-22
• [Presentation] Quantitative analysis of toxin extracts from various tissues of wild and cultured puffer fish by electrophysiological method (2007)
  • Author(s): 佐々木 恵太, 高山 靖規, 伊東 祐之, 赤池 紀生
  • Organizer: 第60回日本薬理学会西南部会
  • Place of Presentation: 宮崎
  • Year and Date: 2007-11-22
• [Presentation] マウス輸精管平滑筋細胞における電位依存性ナトリウムチャネルの電気生理学および分子薬理学的特性に関する検討 (2007)
  • Author(s): 寺本 憲功, 朱 海雷, 相島 真奈美, 伊東 祐之
  • Organizer: 日本薬理学会第80回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-16
• [Presentation] モルモットの排尿筋と大動脈平滑筋における新規ATP感受性カリウムチャネル開口薬、ZD0947に対する効果の比較 (2007)
  • Author(s): 相島 真奈美, 寺本 憲功, 柚木 貴和, 友田 稔久, 朱 海雷, 伊東 祐之
  • Organizer: 日本薬理学会第80回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-16
• [Presentation] サソリ毒、Kurtoxinのマウス輸精管平滑筋細胞における電位依存性ナトリウム電流に及ぼす効果 (2007)
  • Author(s): 朱 海雷, 寺本 憲功, 相島 真奈美, 伊東 祐之
  • Organizer: 日本薬理学会第80回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-16
• [Presentation] マトリックスメタルプロテアーゼ1 による気道平滑筋の収縮能の変化 (2007)
  • Author(s): 太田良紀, 大池正宏, 伊東祐之
  • Organizer: 日本薬理学会第80 回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] ヘパリナーゼIIIは血管内皮細胞の機械刺激応答を阻害する (2007)
  • Author(s): 渡邊未知, 大池正宏, 伊東祐之
  • Organizer: 日本薬理学会第80 回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] 血管内皮上清による血管平滑筋細胞のカルシウム動態の変化 (2007)
  • Author(s): 小西秀平, 渡邊未知, 木村千稚, 大池正宏, 伊東祐之
  • Organizer: 日本薬理学会第80 回総会2007年3月15日
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] マウス輸精管平滑筋細胞における電位依存性ナトリウムチャネルの電気生理学および分子薬理額的特性に関する検討 (2007)
  • Author(s): 寺本憲功, 朱海雷, 相島真奈美, 伊東祐之
  • Organizer: 日本薬理学会第80 回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] モルモットの排尿筋と大動脈平滑筋における新規ATP 感受性ナトリウムチャネル開口薬、ZD0947 に対する効果の比較 (2007)
  • Author(s): 相島真奈美 寺本憲功 柚木貴和 友田稔久 朱海雷 伊東祐之
  • Organizer: 日本薬理学会第80 回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] サソリ毒、Kurtoxinのマウス輸精管平滑筋細胞における電位依存性ナトリウム電流に及ぼす効果 (2007)
  • Author(s): 朱海雷, 寺本憲功, 相島真奈美, 伊東祐之
  • Organizer: 日本薬理学会第80 回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] マトリックスメタロプロテアーゼ1による気道平滑筋の収縮能の変化 (2007)
  • Author(s): 太田 良紀, 大池 正宏, 伊東 祐之
  • Organizer: 日本薬理学会第80回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] ヘパリナーゼIIIは血管内皮細胞の機械刺激応答を阻害する (2007)
  • Author(s): 渡邊 未知, 大池 正宏, 伊東 祐之
  • Organizer: 日本薬理学会第80回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15
• [Presentation] 血管内皮上清による血管平滑筋細胞のカルシウム動態の変化 (2007)
  • Author(s): 小西 秀平, 渡邊 未知, 木村 千稚, 大池 正宏, 伊東 祐之
  • Organizer: 日本薬理学会第80回総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-03-15