Development of preventive and therapeutic method of asthma by the regulation of arginase

• Project/Area Number: 19390163
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Okayama University
• Principal Investigator: OGINO Keiki Okayama University, 大学院・医歯薬学総合研究科, 教授 (70204104)
• Co-Investigator(Kenkyū-buntansha): OU Tatsuko 岡山大学, 大学院・医歯薬学総合研究科, 助教 (90294404) ; TAKIGAWA Tomoko 岡山大学, 大学院・医歯薬学総合研究科, 助教 (90403493) ; MAEKAWA Tuyoshi 山口大学, 大学院・医学系研究科, 教授 (60034972) ; IZUMI Tomonori 山口大学, 医学系研究科, 准教授 (00261694) ; SASAKI Kenji 岡山大学, 大学院・医歯薬学総合研究科, 教授 (20116461) ; OUCHI Kazunobu 川崎医科大学, 医学部, 教授 (80351899)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Kazuyuki 山口大学, 大学院・医学系研究科, 教授 (90107748)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2009: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 環境保健 / 予防医学 / 環境生理 / アルギナーゼ / アルギナーゼ阻害剤 / ステロイド / 喘息 / 呼気NO / 喘息モデル / 一酸化窒素合成酵素 / 一酸化窒素 / 気道抵抗 / NC / Ngaマウス / サイトカイン / ダニ / 一酸化窒素(NO) / 一酸化窒素合成酵素(NOS) / IL-13 / 喘息予防

Research Abstract

We demonstrated that the deletion of nitric oxide as a bronchodilator in asthma was contributed to consumption of arginine and low generation of nitric oxide from nitric oxide synthase from upregulated arginase in mite-induced mice asthma model by inoculation of anti-IL-13 monoclonal antibody and an arginase inhibitor. Moreover, it was demonstrated that in human asthma increased serum arginase levels regulated serum arginine levels and exhaled nitric oxide.

Research Products

• [Journal Article] Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model. (2010)
  • Author(s): Takahashi N, Ogino K, Takemoto K, Hamanishi S, Wang DH, Takigawa T, Shibamori M, Ishiyama H, Fujikura Y
  • Journal Title: Am J Physiol Lung Cell Mol Physiol (in press)
  • Peer Reviewed
• [Journal Article] Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model (2010)
  • Author(s): Takahashi N, Ogino K, Takemoto K, Hamanishi S, Wang DH, Takigawa T, Shibamori M, Ishiyama H, Fujikura Y
  • Journal Title: Am J Physiol Lung Cell Mol Physiol (in press)
  • Peer Reviewed
• [Journal Article] Efficient assay for total antioxidant capacity in human plasma using a 96-well microplate. (2009)
  • Author(s): Kambayashi Y, Binh NT, W Asakura H, Hibino Y, Hitomi Y, Nakamura H, Ogino K
  • Journal Title: J Clin Biochem Nutr 44 Pages: 46-51
  • NAID: 130004466533
  • Peer Reviewed
• [Journal Article] Preparation and Characterization of a Polyclonal Antibody against Brominated Protein. (2009)
  • Author(s): Kambayashi Y, Ogino K, Takemoto K, Imagama T, Takigawa T, Kimura S, Hibino Y, Hitomi Y, Nakamura H.
  • Journal Title: J Clin Biochem Nutr 44(1) Pages: 95-103
  • NAID: 130004466540
  • Peer Reviewed
• [Journal Article] Plasam 3-nitrotyrosine, urinary 8-isoprostane and 8-OHdG among healthy Japannese people (2009)
  • Author(s): Sakano N, Takahashi N, Wang DH, Sauriasari R, Takemoto K, Kanbara S, Sato Y, Takigawa T, Takaki J, Ogino K
  • Journal Title: Free Radic Res 43 Pages: 183-192
  • Peer Reviewed
• [Journal Article] Oxidative stress bimakers and lifestyles in Japanese healthy people. (2009)
  • Author(s): Sakano N, Wang DN, Takahashi N, Wang B, Sauriasari R, Kanbara S, Sato Y, Takigawa T, Takaki J, Ogino K
  • Journal Title: J Clin Biochem Nutr 44 Pages: 185-195
  • Peer Reviewed
• [Journal Article] Preparation and chracterization of a polyclonal antibody. (2009)
  • Author(s): Kambayashi Y, Ogino K, Takemoto K, Imagama T, Takigawa T, Kimura S, Hibino Y, Hitomi Y, Nakamura H
  • Journal Title: J Clin Biochem Nutr 44 Pages: 95-103
  • Peer Reviewed
• [Journal Article] Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice. (2008)
  • Author(s): Fukuoka N, Sugiyama H, Inoue T, Kikumoto Y, Takie K, Morinaga K, Nakano K, Meeshima Y, Asanuma M, Wang DH, Ogino K, Masuoka N, mak i no H
  • Journal Title: Am J Nephrol 28 Pages: 661-668
  • Peer Reviewed
• [Journal Article] Mammalian acatalasemia : the perspectives of bioinfomatics and genetic toxicology. (2008)
  • Author(s): Ogata M, Wang DH, Ogino K
  • Journal Title: Acta Medica Okayama 62 Pages: 345-361
  • Peer Reviewed
• [Journal Article] Assciation between serum gamma-glutamyltransferase and oxidative stress related factors. (2008)
  • Author(s): Takigawa T, Hibino Y, Kimura s, Yamauchi H, Wang BL, Ogino K
  • Journal Title: Heapto-gastroenterology 55 Pages: 50-53
  • Peer Reviewed
• [Journal Article] Biomarkers of oxidative/nitrosative stress: an approach to disease prevention. (2007)
  • Author(s): Ogino K, Wang DH
  • Journal Title: Acta Med Okayama. 61 Pages: 181-189
  • NAID: 120002311692
  • Peer Reviewed
• [Journal Article] Biochemical characterization of reactive nitrogen species by eosinophil peroxidase in tyrosine nitration. (2007)
  • Author(s): Takemoto K, Ogino K, Wang DH, Takigawa T, Kurosawa CM, Kamyabashi Y, Hibino Y, Hitomi Y, Ichimura H
  • Journal Title: Acta Med Okayama 61 Pages: 17-30
  • NAID: 120002312059
  • Peer Reviewed
• [Journal Article] Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma. (2007)
  • Author(s): Takemoto K, Ogino K, Shibamori M, Gondo T, Hitomi Y, Takigawa T, Wang DH, Takaki J, Ichimura H, Fujikura Y, Ishiyama H
  • Journal Title: Am J Physiol Lung Cell Mol Physiol 293
  • Peer Reviewed
• [Journal Article] NC/Ngaマウス喘息モデルの特徴. (2007)
  • Author(s): 荻野景規
  • Journal Title: 喘息 22 Pages: 40-43
  • Peer Reviewed
• [Journal Article] 3-ニトロチロシン (2007)
  • Author(s): 荻野景規
  • Journal Title: 岡山医学会雑誌 118 Pages: 225-234
  • NAID: 10018454166
  • Peer Reviewed
• [Journal Article] Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma. (2007)
  • Author(s): Takemoto K, Ogino K, Shibamori M, Gondo T, Hitomi Y, Takigawa T, Wang DH, Takaki J, Ichimura H. Fuiikura Y. Ishivama H.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. 293
  • Peer Reviewed
• [Journal Article] Biochemical characterization of reactive nitrogen species by eosinophil peroxidase in tyrosine nitration. (2007)
  • Author(s): Takemoto K, Ogino K, Wang DH, Takigawa T, Kurosawa CM, Kamyabashi Y,Hibino Y, Hitomi Y. Ichimura H.
  • Journal Title: Acta Med Okayama. 61 Pages: 17-30
  • NAID: 120002312059
  • Peer Reviewed
• [Journal Article] Disposition of protein-bound 3-nitrotyrosine in rat plasma analysed by a novel prolocol for HPLC-ECD. (2007)
  • Author(s): Hitomi YH, Okuda J, Nishino H, Kambayashi Y, Hibino Y, Takemoto K, Takigawa T, Ohno H. Taniguchi N. Ogino K..
  • Journal Title: J Biochem. 141 Pages: 495-502
  • Peer Reviewed
• [Journal Article] Genotypes and haplotypes of CCR2 and CCR3 genes in Japanese cedar pollinosis. (2007)
  • Author(s): Nakamura H, Higashikawa F, Nobukuni Y, Miyagawa K, Endo T, Imai T, Hatta K, Ozasa K, Motohashi Y, Matsuzaki I, Sasahara S, Ogino K, Akimaru K, Eboshida A.
  • Journal Title: Int Arch Allergy Immunol. 142 Pages: 329-334
  • Peer Reviewed
• [Presentation] Markers of oxidative/nitrosative stress and inflammation in cigarette smoking-induced pre-clinical stage of renal dysfunction in general population. (2009)
  • Author(s): ラニサウリアサリ、汪達紘、坂野紀子、高木二郎、竹本圭、中村裕之、王柄玲、杉山斉、人見嘉哲、佐藤美恵、高橋紀子、瀧川智子、神原咲子、荻野景規
  • Organizer: 第7回日本予防医学会学術総会
  • Place of Presentation: 千葉市
  • Year and Date: 2009-12-13
• [Presentation] アルギナーゼ阻害による実験的喘息の抑制 (2009)
  • Author(s): 高橋紀子、竹本圭、濱西誠司、ラニサウリアサリ、柴森雅文、汪達紘、瀧川智子、高木二郎、石山広信、荻野景規
  • Organizer: 第79回日本衛生学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 2009-03-31
• [Presentation] アルギナーゼ欠損マウスにおける実験的潰瘍性大腸炎症状の評価 (2009)
  • Author(s): 赤澤裕二、荻野景規、竹本圭、汪達紘、高橋紀子、高木二郎、瀧川智子
  • Organizer: 第79回日本衛生学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 2009-03-31
• [Presentation] アルギナーゼ阻害による実験的喘息の抑制 (2009)
  • Author(s): 高橋紀子, 竹本圭, 濱西誠司, ラニサウリアサリ, 柴森雅文, 王達紘, 瀧川智子, 高木二郎, 石山広信, 荻野景規
  • Organizer: 第79回日本衛生学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-31
• [Presentation] カタラーゼ投与による実験的潰瘍性大腸炎症の緩和 (2009)
  • Author(s): 赤澤裕二、荻野景規、竹本圭、汪達紘、瀧川智子
  • Organizer: 第7回日本予防医学会学術総会
  • Place of Presentation: 千葉市
• [Presentation] ダニ蛋白誘発喘息におけるステロイド剤の効果;NOとアルギナーゼの関係 (2009)
  • Author(s): 宗友一晃、竹本圭、吉田純子、張燃、鄒宇、瀧川智子、汪達紘、高木二郎、荻野景規
  • Organizer: 第7回日本予防医学会学術総会
  • Place of Presentation: 千葉市
• [Presentation] アルギナーゼの特異的な阻害剤であるNor-NOHAの喘息モデルMc/Ngaマウスへの投与による効果 (2008)
  • Author(s): 濱西誠司、竹本圭、高橋紀子、ラニサウリアサリ、柴森雅文、汪達紘、荻野景規
  • Organizer: 第6回日本予防医学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 2008-11-30
• [Presentation] アルギナーゼの特異的な阻害剤であるNor-NOHAの喘息モデルMc/Ngaマウスへの投与による効果 (2008)
  • Author(s): 濱西誠司, 竹本圭, 高橋紀子, ラニサウリアサリ, 柴森雅文, 汪達紘, 荻野景規
  • Organizer: 第6回日本予防医学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-30
• [Presentation] 喘息増悪因子としてのアルギナーゼ誘導-NC/Ngaマウス喘息モデルを用いた検討 (2008)
  • Author(s): 竹本圭、黒澤カルメン、濱西誠司、柴森雅文、高木二郎、瀧川智子、汪達紘、荻野景規
  • Organizer: 第8回日本NO学会学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 2008-05-10
• [Presentation] 喘息増悪因子としてのアルギナーゼ誘導一NC/Ngaマウス喘息モデルを用いた検討 (2008)
  • Author(s): 竹本圭, 黒沢カルメン, 濱西誠司, 柴森雅文, 高木二郎, 瀧川智子, 王達紘, 荻野景規
  • Organizer: 第8回日本NO学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2008-05-10
• [Presentation] IL-13モノクローナル抗体によるアルギナーゼI阻害はHC/Ngaマウスのアレルギー喘 (2008)
  • Author(s): 黒沢カルメン、柴森雅文、石山広信、竹本圭、王 炳玲、演西誠司、Rani Sauriasari、瀧川智子、汪 達紘、高木二郎、荻野景規
  • Organizer: 第78回日本衛生学会総会
  • Place of Presentation: 熊本市、熊本市民会館
  • Year and Date: 2008-03-31
• [Presentation] NOの枯渇は、喘息の病態に重要な影響をもたらすか? (2007)
  • Author(s): 竹村洋子、竹本圭、瀧川智子、汪達紘、荻野景規
  • Organizer: 第7回日本NO学会学術集会
  • Place of Presentation: 大津市、ピアザ淡海
  • Year and Date: 2007-05-17
• [Presentation] IL-13モノクローナル抗体によるアルギナーゼi阻害はNC/Ngaマウスのアレルギー喘息様反応を抑制する (2007)
  • Author(s): 黒沢カルメン、柴森雅文、石山広信、竹本圭、王炳玲、濱西誠司、ラニサウリアサリ、瀧川智子、汪達紘、高木二郎、荻野景規
  • Organizer: 第78回日本衛生学会
  • Place of Presentation: 熊本市
  • Year and Date: 2007-03-31
• [Presentation] NOの枯渇は喘息の病態に重要な影響をもたらすか? (2007)
  • Author(s): 竹村洋子、竹本圭、瀧川智子、汪達紘、荻野景規
  • Organizer: 第7回日本NO学会学術集会
  • Place of Presentation: 大津市