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Treatment of acute lung injury by inhibition of gene induction of NO synthase in alveolar macrophages.

Research Project

Project/Area Number 12670579
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTokyo Woman's Medical University

Principal Investigator

TAMAOKI Jun  Tokyo Women's Medical University Depertment of Medicine, Assc Prof., 医学部, 助教授 (60147395)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsMacrophage / Nitric Oxide / Gene therapy / Lung injury / Cytokines / Macrolide / Erythromycin / Clarithromycin / 遺伝子治療 / 急性肺傷害 / クラリスロマイシン / ポーラログラフィー
Research Abstract

Macrolide antibiotics have unique immunomodulatory actions apart from antimicrobial properties. We studied the effects of macrolides on immunoglobulin G immune complex (IgG-ICx)-induced lung injury in rats in vivo and in vitro. Intrapulmonary deposition of IgG-ICx produced a time-dependent increase in the concentration of NO in exhaled air. There were corresponding increases in the number of neutrophils accumulated into alveolar spaces, and lung wet-to-dry weight ratio. All of these changes were inhibited by pretreatment with erythromycin or josamycin, but not by amoxicillin or cephaclor. Incubation of cultured pulmonary alveolar macrophages (PAM) caused upregulation of NO production and expression of inducible NO synthase (iNOS) mRNA, an effect that was dose dependently inhibited by erythromycin, roxithromycin, or josamycin. The macrolides also reduced IgG-ICx-induced release of IL-1* and TNF-α, but did not alter the release of NO induced by exogenously added IL-1β and TNF-α. These results suggest that macrolide antibiotics specifically inhibit immune complex-induced lung injury presumably by inhibiting cytokine release and the resultant downregulation of iNOS gene expression and NO production by rat PAM.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 玉置 淳: "呼吸器疾患とマクロライド療法"分子呼吸器病. 4. 413-418 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaoki Jun: "Impairment of airway mucociliasy transport in patient with sinobronchial syndrome"Journal of aerosol Medicine. 13. 239-244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 玉置 淳: "IgG免疫複合体(IgG-ICx)肺傷害モデルに対するマクロライドの効果と作用機序"Japanese Journal of Antibiotics. 54. 83-86 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaoki Jun: "Molecular mechanism of airway remodeling in asthma"Recent Research Developments in Clinical Immunology. 4. 1-10 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 玉置 淳: "気管支・肺の防御機構と呼吸器疾患"埼玉県医学会雑誌. 36. 154-158 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaoki J: "Impairment of airway mucociliary transport in patients with sinobronchial syndrome."J Aerosol Med. 13. 239-244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaoki J: "Effects of macrolides on lung injufy induced by lgG immune complex."Jap J Antibiot. 54. 83-86 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaoki J: "Molecular mechanisms of airway remodeling in asathma."Recent Res Dev Clin Immunol. 4. 1-10 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tagaya E: "Effect of short-term clarithromycin therapy in patients with airway hypersecretion."Jap J Antibiot. 54. 33-35 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaoki Jun: "Molecular mechanism of airway remodeling in asthma"Recent Research Developments in Clinical Immunology. 4. 1-10 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 多賀谷悦子: "気道分泌亢進に対するクラリスロマイシン短期投与の効果"Japanese Journal of Antibiotics. 54. 33-35 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 玉置 淳: "気管支・肺の防御機構と呼吸器疾患"埼玉県医学会雑誌. 36. 154-158 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 玉置淳: "呼吸器疾患とマクロライド療法"分子呼吸器病. 4. 413-418 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tamaoki Jun: "Impairment of airway mucociliary transport in patients with sinobronchial syndrome"Journal of Aerosol Medicine. 13. 239-244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 玉置淳: "IgG免疫複合体(IgG-ICx)肺傷害モデルに対するマクロライドの効果と作用機序"Japanese Journal of Antibiotics. 54. 83-86 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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