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Determination of the contributory factors for the development of allergic airway inflammation in a murine model of infantile asthma.

Research Project

Project/Area Number 13670784
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionGunma University

Principal Investigator

TOKUYAMA Kenichi  Gunma University Fac.of Med., Dept. of Pediatrics Associate Professor, 医学部, 助教授 (30237078)

Co-Investigator(Kenkyū-buntansha) ARAKAWA Hirokazu  Gunma University Fac.of Med., Dept. of Pediatrics Assistant Professor, 医学部, 助手 (50272232)
MOCHIZUKI Hiroyuki  Gunma UniversHy Fac.of Med., Dept. of Pediatrics Associate Professor, 医学部, 講師 (50270856)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsairway inflammation / mucus secretion / bronchial responsivene / infants / 卵白アルブミン / 幼若マウス / 好酸球 / 粘液分泌細胞 / 気道過敏性
Research Abstract

Clinical features of asthma in infants differ from those in older patients. This may have been partly caused by age-dependent differences in the immune response. Thus, we examined the characteristic features of allergic airway inflammation of infantile asthma by developing a murine model. In adult mice, the sensitizing dose of antigen is known to be critical to the development of polarized helper T cell subsets, and of allergic airway inflammation. Thus, we sensitized animals of different stages of maturation with different doses of antigen, in order to observe a maturational changes in airway responses under different immunological conditions. Juvenile or adult BALB/C mice were sensitized with low or high doses of ovalbumin (OVA) or vehicle. Animals were, then, challenged with aerosolized OVA or normal saline once a day during 6 consecutive days. After the final challenge, bronchial hyperresponsiveness (BHR), the number of cells in bronchoalveolar lavage fluid (BALF), histological analysis of airways, and serum OVA-specific antibody levels were determined. IL-4 and IFN-γ levels in BALF were also examined. Sensitization with the low dose, but not high dose, OVA induced a Th2 dominant condition (elevated IL-4 and decreased IFN-γ levels) in both age. In both age, BHR, BALF eosinophilia, the cellular infiltration, goblet cell metaplasia (GCM), and IgE antibody levels were more prominent in mice sensitized with the low dose than in those with high dose. Among these responses, only GCM was more remarkable in juvenile mice than in adult animals, whereas inverse relation was the case for other parameters. These results indicate that GCM, and consequently, mucus hypersecretion may be an important component of allergic airway inflammation of juvenile animals.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Tokuyama K, Nishimura H, et al.: "Effect of Y-27632, a Rho/ Rho-kinase inhibitor, on LTD4-and histamine -induced airflow obstruction and airway microvascular leakage in guinea pigs in vivo"Pharmacology. 64. 189-195 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura H, Tokuyama K, et al.: "Airways responsiveness and airway remodeling after chronic exposure to procaterol and fenoterol in guinea pigs in vivo"Int Arch Allergy Immunol. 129. 320-326 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohki Y, Tokuyama K, et al.: "Maturational changes in airway remodeling after chronic exposure to ovalbumin in sensitized guinea pigs : Role of the cell renewal of airway resident cells"Pediatr Res.. 52. 525-532 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue Y, Tokuyama K, et al.: "Effects of STA2, a thromboxane A2 mimetic, in inducing airflow obstruction and airway microvascular leakage in guinea pigs"Pharmacology. 65. 62-68 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato M, Tokuyama K, et al.: "Increased superoxide radicals generation from alveolar macrophages in immature guinea-pigs"Cell Biol Int. 26. 829-832 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 徳山研一: "小児喘息は成人喘息のミニチュアか?-気道炎症・気道リモデリングの側面から-"日本小児アレルギー学会誌. 16. 131-136 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tokuyama K, Nishimura H, lizuka K, Kato M, Arakawa H, Saga R, Mochizuki H, Morikawa A.: "Effect of Y-27632, a Rho/ Rho-kinase inhibitor, on leukotriene D4- and histamine-induced airflow obstruction and airway microvascular leakage in guinea pigs in vivo."Pharmacology. 64. 189-195 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura H, Tokuyaina K, Arakawa H, Ohki Y, Sato A, Kato M, Mochizuki H, Morikawa A.: "Airways responsiveness and airway remodeling after chronic exposure to procaterol and fenoterol in guinea pigs in vivo"Int Arch Allergy Immunol. 129. 320-326 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohki Y, Tokuyama K, Sato A, Nishimura H, Tabata M, Tomiyoshi K, Inoue T, Arakawa H, Kato M, Mochizuki H, Morikawa A.: "Maturational changes in airway remodeling after chronic exposure to ovalbumin in sensitized guinea pigs : Role of the cell renewal of airway resident cells"Pediatr Res. 52. 525-532 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato M, Tokuyama K, Minakami H, Nagai A, Kozawa K, Goto H, Morikawa A, Kimura H.: "Increased superoxide radicals generation from alveolar macrophages in immature guinea-pigs"Cell Biol Int. 26. 829-832 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue Y, Tokuyama K, Nishimura H, Arakawa H, Kato M, Mochizuki H, Morikawa: "Effects of STA2, a thromboxane A2 mimetic, in inducing airflow obstruction and airway microvascular leakage in guinea pigs"Pharmacology. 65(2). 62-68 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takizawa T, Kato M, Kimura H, Suzuki M, Tachibana A, Obinata H, Izumi T, Tokuyama K, Morikawa A.: "Inhibition of protein kinase A and C demonstrates dual modes of response in human eosinophils stimulated with platelet-activating factor"J Allerg Clin Immunol. 110. 241-248 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mirza ZN, Kato M, Kimura H, Tachibana A, Fujiu T, Suzuki M, Mochizuki H, Tokuyama K, Morikawa A.: "Fenoterol inhibits suproxide anion generation by human polymorphonuclear leukocytes via β2-adrenoreceptor-dependent and -independent mechanisms"Ann Allergy Asthma Immunol. 88. 494-500 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arakawa H, Takizawa T, Tokuyama K, Mochizuki H, Morikawa A.: "Efficacy of inhaled anticholinergics and anesthesia in treatment of a patient in status asthmatics"J Asthma. 39. 77-80 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mochizuki H, Ohki Y, Arakawa H, Kato M, Tokuyama K, Morikawa A.: "Effect of inhaled indomethacin on distilled water-induced airway epithelial cell swelling"J Appl Physiol. 92. 155-161 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura K, Arakawa H, Suzuki M, Kobayashi Y, Mochizuki H, Kato M, Tokuyama K, Morikawa A.: "Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associaetd with allergic diseases"Clin Exp Allergy. 31. 1509-1514 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura H, Tokuyama K, Inoue Y, Arakawa H, Kato M, Mochizuki H, Morikawa A.: "Acute effects of prostaglandin D2 to induce airflow obstruction and airway microvascular leakage in guinea pigs : role of thromboxane A2 receptors"Prostag Oth Lipid M. 66. 1-15 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohki Y, Kato M, Kimura H, Nako Y, Tokuyama K, Morikawa A.: "Elevated type IV collagen in bronchoalveolar lavage fluid from infants with bronchopulmonary dysplasia"Biol Neonate. 74. 34-38 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tokuyama K, Nishimura H et al.: "Effect of Y-27632, a Rho/ Rho-kinase inhibitor, on LTD4-and histamine -induced airflow obstruction and airway microvascular leakage in guinea pigs in vivo"Pharmacology. 64. 189-195 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishimura H, Tokuyama K et al.: "Airways responsiveness and airway remodeling after chronic exposure to procaterol and fenoterol in guinea pigs in vivo"Int Arch Allergy Immunol. 129. 320-326 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohki Y, Tokuyama K et al.: "Maturational changes in airway remodeling after chronic exposure to ovalbumin in sensitized guinea pigs : Role of the cell renewal of airway resident cells"Pediatr Res.. 52. 525-532 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue Y, Tokuyama K et al.: "Effects of STA2, a thromboxane A2 mimetic, in inducing airflow obstruction and airway microvascular leakage in guinea pigs"Pharmacology. 65. 62-68 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato M, Tokuyama K et al.: "Increased superoxide radicals generation from alveolar macrophages in immature guinea-pigs"Cell Biol Int. 26. 829-832 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 徳山研一: "小児喘息は成人喘息のミニチュアか?-気道炎症・気道リモデリングの側面から-"日本小児アレルギー学会誌. 16. 131-136 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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