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Pathogenic role of a novel vhloride channel on mucus hypersecretion in the airways of the patients with asthma

Research Project

Project/Area Number 13670613
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionDokkyo University School of Medicine

Principal Investigator

TODA Masao  Dokkyo University, School of Medicine, Assistant Professor, 医学部, 講師 (50175478)

Co-Investigator(Kenkyū-buntansha) SAGARA Hironori  Dokkyo University, School of Medicine, Assistant Professor, 医学部, 講師 (80275742)
FUKUSHIMA Yasutsugu  Dokkyo University, School of Medicine, Assistant Professor, 医学部, 講師 (00254996)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsbronchial asthma / airway wall remodeling / airway epithelial cells / chloride channel / interleukin-9 / interleukin-9 recepter / human calcium-activated chloride channel 1 (HCLCA1) / 慢性気管支炎 / サルコイドーシス / 気道分泌
Research Abstract

One of the cardinal features of airway remodeling in asthrnais mucus gland hyperplasia and mucus overproduction and hypersecretion. Recently, a calcium-activated chloride channel, HCLCA1, was described that is upregulated by IL-9 and thought to regulate the expression of macros, such as MUCSA/C, a critical component of mucus in the airways.
We examined the expression of HCLCA1 in bronchial biopsy specimens of asthmatic subjects compared with those of control subjects and to demonstrate its relationship with IL-9, IL-9 receptor (IL-9R), and markers of mucus production. Bronchial biopsy specimens from subjects with asthmatic (n = 9), chronic bronchitis (n =10), sarcoidosis (n = 8) and healthy control (n =10) were stained with periodic acid-Schiff (PAS) to identify mucus glycoconjugates. IL-9-and IL-9R-positive cells were identified with in immunocytochemistly, and HCLCAI expression was detected by means of in situ hybridization with cRNA probes. We demonstrate significant increases in IL- … More 9 (P <.001) and IL-9R (P <.05) immunoreactivity, as well as increased expression of HCLCAL mRNA (P <.001), in the epithelium of asthmatic patients compared with that found in control subjects. There was also an increase in the number of mucus-producing cells in biopsy specimens from asthmatic subjects (P<.001). HCLCA1 mRNA was strongly and selectively colocalized with PAS and IL-9R-positive epithelial cells. In particular, a strong positive correlation was observed between HCLCAI mRNA expression and IL-9-positive (r = 0.69, P <0.01) or 1L9R-positive (r = 0.79, P <.01) cells. An upregulation of HCLCA1 in the IL-9-responsive mucus-producing epithelium of asthmatic subjects compared with that seen in control subjects supports the hypothesis that this channel may be responsible, in part, for the overproduction of mucus in asthmatic subjects. These preliminary findings suggest the inhibition of HCLCAI may be an important new therapeutic approach to control mucus overproduction in chronic airway disorders. Less

Report

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

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Masao Toda, et al.: "A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma"Journal of Allergy and Clinical Immunology. 109. 246-250 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Toda, et al.: "Is ICACC, a novel chloride channel, expressed within airway subepithelium of asthmatic patients implicated in mucus production?"American Journal of Respiratory and Critical Care Medicine. 165. A812 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] E.Nutku, M.Toda, Q.A.Hamid: "Rhinitis, nasal polyposis and asthma : pathological aspects. The Nose and Lung Diseases. European Respiratory Monograph. vol 6, No 18"European Respiratory Society Journal Ltd. 115-142 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toda, M., et al.: "A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma"J Allergy Clin Immunol. 109. 246-250 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toda, M., et al.: "Is ICACC, a novel chloride channel, expressed within aitway subepithelium of asthmatic patients implicated in mucus production?"Am J Respir Crit Care Med. 165. A812 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nutku, E., Toda, M., Hamid, Q.A.: "Rhinitis, nasal polyposis and asthma pathological aspects. The Nose and Lung Diseases. European Respiiatoiy Monograph. vol 6,no.18"European Respiratory Society Journal Ltd, Sheffield. 115-142 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masao Toda, Meri K Tulic, Roy C Levitt, Qutayba Hamid: "A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patient with asthma"J Allergy Clin Immunol. 109・2. 246-250 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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