MECHANISMS OF BIOLOGICAL EFFECTS OF HUMAN AIRWAY TRYPSIN-LIKE PROTEASE (HAT) ON BRONCHIAL CELLS AND PATHOLOGICAL ROLES OF HAT IN THE AIRWAY DISEASES
| Project/Area Number |
13557052
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MAEZAWA Hiroshi THE UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (00138653)
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| Co-Investigator(Kenkyū-buntansha) |
HOUTI Hitoshi THE UNIVERSITY OF TOKUSHIMA, UNIVERSITY HOSPITAL, ASSOCIATE PROFESSOR, 医学部歯学部附属病院, 助教授 (00219156)
KOYAMA Hajime THE UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80109074)
SANO Toshiaki THE UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80154128)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | Human airway trypsin-like protease / Chronic airway disease / IL-8 / Bronchial epithelial cells / Bronchial fibroblasts / PAR-2 / Cell proliferation / MAP kinase / EGFR / 肥満細胞性トリプターゼ / IL-8 / 気道上皮細胞 / PAR-2 agonist / カルシウムイオン / 肺線維芽細胞 / PAR2 / カルシウムイオン(Ca^<2+>) |
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| Research Abstract |
1. Contents of human airway trypsin-like protease (HAT) in sputum : There was no difference between HAT concentration in sputum from healthy volunteers and that from patients with chronic airway diseases. Because the patients have more abundance of secretion of bronchial lavage fluid than healthy volunteers, it is considered that the production of HAT in airway of patients is enhanced and HAT causes the progress and amplification of disease
2. Mechanisms of proliferation enhanced by HAT on normal human bronchial fibroblasts : HAT enhanced proliferation of bronchial fibroblasts in serum-free medium with or without transferrin. Protease-activated receptor-2 agonist peptide (PAR2AP) enhanced proliferation of bronchial fibroblasts in serum-supplemented medium with transferrin. Leupeptin (serine protease inhibitor) and U0126 (MEK inhibitor) inhibited HAT induced proliferation of bronchial fibroblasts. Western blot analysis showed that HAT promoted the phosphorylation of MAP kinase. It was concluded that HAT enhanced the proliferation of fibroblasts through MAP kinase signal transduction, but not through PAR2
3. Enhanced synthesis of IL-8 by HAT on human bronchial epithelial cells (HBEC) : PAR2 mRNA was detected in HBEC with reverse PCR. Induction of IL-8 mRNA and release of IL-8 were increased by addition of HAT and PAR2 agonist peptide on HBEC. It was concluded that enhancement of IL-8 synthesis by HAT on HBEC was resulted from a sequential activation process : PAR2 activation by HAT, EGFR activation by transactivation and MAP kinase activation
4. Activation of PAR2 by HAT on bronchial epithelial cells : Activation of PAR which coupled with G-protein increases the concentration of free Ca^<2+> in cells. Concentration of free Ca^<2+> in HBEC was increased by stimulation of HAT and PAR2 agonist peptide. It was concluded that HAT controlled the metabolic function of HBEC through activation of PAR2
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Report
(4 results)
Research Products
(3 results)
