Role of MMPs in refractory asthma

• Project/Area Number: 22790766
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: ICHIKAWA Tomohiro 和歌山県立医科大学, 医学部, 助教 (20405450)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 閉塞性肺疾患 / 気管支喘息 / MMP / iNOS / 慢性閉塞性肺疾患 / 肺線維芽細胞 / NF-κB / IRF-3 / リモデリング / 難治性喘息 / 気道リモデリング / テオフィリン / 窒素化ストレス / NF-kB / TGF-β1 / HDAC / TIMP / ステロイド抵抗性

Research Abstract

Because it is well known that airway remodeling contributes to the refractoriness of asthma and MMPs play an important role in the formation of remodeling, we explored the factors that affect the production and activation of matrix metalloproteinase (MMPs) by lung fibroblast, one of the main producer of MMPs in the lung. We found that peroxynitrite, one of the potent oxidants, and activation of toll like receptor (TLR)-3 are the contributors of excessive MMP production and activation by lung fibroblasts. These results suggest that reactive nitrogen species and the TLR3 pathway are related with MMP-mediated airway remodeling.

Research Products

• [Journal Article] 25-hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway. (2013)
  • Author(s): Ichikawa T, Sugiura H, Koarai A, Kikuchi T, Hiramatsu M, Kawabata H, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M.
  • Journal Title: Exp Cell Res Volume: 319 Pages: 1176-86
  • Peer Reviewed
• [Journal Article] 25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway (2013)
  • Author(s): Tomohiro Ichikawa
  • Journal Title: Experimental Cell Research Volume: 319 Issue: 8 Pages: 1176-1186
  • DOI: 10.1016/j.yexcr.2013.02.014
  • Peer Reviewed
• [Journal Article] 25-Hydroxycholesterol enhances cytokine release and Toll-like receptor 3 response in airway epithelial cells. (2012)
  • Author(s): Koarai A, Yanagisawa S, Sugiura H, Ichikawa T, Kikuchi T, Furukawa K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M.
  • Journal Title: Respir Res. Volume: 13
  • Peer Reviewed
• [Journal Article] Cigarette smoke augments the expression and responses of toll-like receptor 3 in human macrophages. (2012)
  • Author(s): Koarai A, Yanagisawa S, Sugiura H, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M.
  • Journal Title: Respirology Volume: 17 Pages: 1018-25
  • Peer Reviewed
• [Journal Article] Associated demographics of persistent exhaled nitric oxide elevation in treated asthmatics. (2012)
  • Author(s): Matsunaga K, Yanagisawa S, Hirano T, Ichikawa T, Koarai A, Akamatsu K, Sugiura H, Minakata Y, Matsunaga K, Kawayama T, Ichinose M.
  • Journal Title: Clin Exp Allergy Volume: 42 Pages: 775-81
  • Peer Reviewed
• [Journal Article] Validation of the triaxial accelerometer for the evaluation of physical activity in Japanese patients with COPD. (2012)
  • Author(s): Kanda M, Minakata Y, Matsunaga K, Sugiura H, Hirano T, Koarai A, Akamatsu K, Ichikawa T, Ichinose M.
  • Journal Title: Intern Med Volume: 51 Pages: 369-75
  • NAID: 130002062007
  • Peer Reviewed
• [Journal Article] Increased 25-hydroxycholesterol concentrations in the lungs of patients with chronic obstructive pulmonary disease. (2012)
  • Author(s): Sugiura H, Koarai A, Ichikawa T, Minakata Y, Matsunaga K, Hirano T, Akamatsu K, Yanagisawa S, Furusawa M, Uno Y, Yamasaki M, Satomi Y, Ichinose M.
  • Journal Title: Respirology Volume: 17 Pages: 533-40
  • Peer Reviewed
• [Journal Article] Inhibitory effects of theophylline on the peroxynitrite-augmented release of matrix metalloproteinases by lung fibroblasts. (2012)
  • Author(s): Sugiura H, Kawabata H, Ichikawa T, Koarai A, Yanagisawa S, Kikuchi T, Minakata Y, Matsunaga K, Nakanishi M, Hirano T, Akamatsu K, Furukawa K, Ichinose M.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: 302
  • Peer Reviewed
• [Journal Article] Increase of 27-hydroxycholesterol in the airways of patients with COPD: possible role of 27-hydroxycholesterol in tissue fibrosis. (2012)
  • Author(s): Kikuchi T, Sugiura H, Koarai A, Ichikawa T, Minakata Y, Matsunaga K, Nakanishi M, Hirano T, Akamatsu K, Yanagisawa S, Furukawa K, Kawabata H, Ichinose M.
  • Journal Title: Chest Volume: 142 Pages: 329-37
  • Peer Reviewed
• [Journal Article] Inhibitory effects of theophylline on the peroxynitrite-augmented release of matrix metalloproteinases by lung fibroblasts. (2012)
  • Author(s): Sugiura H
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: 302 Issue: 8 Pages: 764-774
  • DOI: 10.1152/ajplung.00342.2011
  • Peer Reviewed
• [Journal Article] Increase of nitrosative stress in patients with eosinophilic pneumonia. (2011)
  • Author(s): Furukawa K, Sugiura H, Matsunaga K, Ichikawa T, Koarai A, Hirano T, Yanagisawa S, Minakata Y, Akamatsu K, Kanda M, Nishigai M, Ichinose M.
  • Journal Title: Respir Res Volume: 17
  • Peer Reviewed
• [Journal Article] High COPD prevalence in patients with liver disease. (2010)
  • Author(s): Minakata Y, Ueda H, Akamatsu K, Kanda M, Yanagisawa S, Ichikawa T, Koarai A, Hirano T, Sugiura H, Matsunaga K, Ichinose M.
  • Journal Title: Intern Med. Volume: 49 Pages: 2687-91
  • NAID: 130000413428
  • Peer Reviewed
• [Presentation] Toll 様受容体 3の活性化は誘導型 NO合成酵素の発現を介して肺線維芽細胞からの matrix metalloproteinase の産生を亢進する. (2013)
  • Author(s): 市川 朋宏
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2013-04-21
• [Presentation] COPD肺における25-hydroxycholesterolの産生と生物学的作用についての検討 (2013)
  • Author(s): 市川 朋宏
  • Organizer: 第9回呼吸器バイオマーカー研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-02
• [Presentation] 25-hydroxycholesterolは肺線維芽細胞に作用して気道リモデリングを促進する. (2011)
  • Author(s): 市川 朋宏
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
• [Presentation] 25-hydroxycholesterolは肺線維芽細胞に作用して気道リモデリングを促進する (2011)
  • Author(s): 市川朋宏
  • Organizer: 第51回日本呼吸器学会
  • Place of Presentation: (東日本大震災のため誌面のみ)
• [Presentation] Peroxynitrite augments fibroblast-mediated tissue remodeling through NF-κB activation (2010)
  • Author(s): Tomohiro Ichikawa
  • Organizer: The 6^<th> International Conference on the Biology, Chemistry, and Therapeutic Application of Nitric Oxide
  • Place of Presentation: Kyoto International Conference Center, Kyoto
  • Year and Date: 2010-06-18
• [Book] COPD 大規模臨床研究の全容 (2012)
  • Author(s): 市川 朋宏, 一ノ瀬 正和
  • Publisher: 医薬ジャーナル社
• [Book] 日本胸部臨床 (2011)
  • Author(s): 市川 朋宏, 一ノ瀬 正和
  • Publisher: 克誠堂出版
• [Book] 日本胸部臨床 (2011)
  • Author(s): 市川朋宏
  • Total Pages: 11
  • Publisher: 克誠堂出版
• [Book] アレルギー・免疫 (2010)
  • Author(s): 市川 朋宏, 杉浦 久敏
  • Publisher: 医薬ジャーナル社
• [Book] アレルギー・免疫17巻12号 (2010)
  • Author(s): 市川朋宏
  • Publisher: 医薬ジャーナル社