2000 Fiscal Year Final Research Report Summary
BIOSYNTHESIS OF RECOMBINANT TRYPTASE FOUND IN THE AIRWAY, AND ITS APPLICATION OF DIAGNOSIS AND THERAPY OF DISEASE
| Project/Area Number |
10557057
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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 |
YASUOKA Susumu THE UNIVERSITY OF TOKUSHIMA, DEPARTMENT OF NURSINNG PROFESSOR, 医療技術短期大学部, 教授 (30035414)
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| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Hajime THE UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICINE ASSITENT PROFESSOR, 医学部, 助教授 (80109074)
SANO Toshiaki THE UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICINE PROFESSOR, 医学部, 教授 (80154128)
MASUDA Kenici TEIJIN INSTITUTE FOR BIOMEDICAL RESEARCH, 創薬第2研究所, 主任研究員
NAKAMURA Yoichi THE UNIVERSITY OF TOKUSHIMA, HOSPITAL OF SCHOOL OF MEDICINE LECTURER, 医学部・附属病院, 講師 (00237447)
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| Project Period (FY) |
1998 – 2000
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| Keywords | HUMAN AIRWAY TRYPSIN-LIKE PROTEASE / BIOSYNTHESIS OF RECOMBINANT PROTEIN / ACTIVATION OF PROUROKINASE / AIRWAY EPITHELIAL CELLS / INTERLEUKIN-8 / ACTIVATION OF FIBRINOLYTIC CASCADE / FIBROBLAST / TGF-β1 |
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| Research Abstract |
IN ORDER TO CLARIFY PATHOPHYSIOLOGICAL SIGNIFICANCE OF HUMAN AIRWAY TRYPSIN-LIKE PROTEASE(HAT), WHICH WE FOUND IN THE HUMAN AIRWAY, IN AIRWAY INFLAMATION.FOLLOWING RESERCHES WERE CARRIED OUT.
1. LOCALIZATION OF HAT IN AIRWAYS : LOCALIZATION OF HAT IN THE AIRWAYS WAS IMMUNOHISTOCHEMICALLY EXAMINED USING FRESH BRONCHIAL TISSUES OBTAINED AT SURGERY.IT WAS SHOWN THAT POSITIVE REACTION WAS FOUND IN BRONCHIAL EPITHELIAL TISSUES.THIS RESULT INDICATES THAT HAT IS BIOSYNTHESIZED IN AIRWAY EPITHELIAL CELLS.
2. ABILITY TO HYDROLYZE ENDOGENOUS PROTEINS OF HAT : IT WAS SHOWN BY SDS-POLYACRYLAMIDE GEL ELECTROPHORESIS THAT HAT CONVERTS PROUROKINASE INTO UROKINASE BY LIMITED PROTEOLYSIS, AND THAT HAT CLEAVES FIBRINOGEN, ESPECIALLY ITS α-CHAIN.
3. EFFECT OF HAT ON NORMAL HUMAN AIRWAY EPITHELIAL CELLS(NHBEC) : IT WAS SHOWN IN VITRO SYSTEM THAT HAT ENHANCES PRODUCTION OF INTERLEUKIN-8 AND GM-CSF BY NHBEC, AND THIS ACTION IS MEDIATED BYACTIVATION OF ROTEASE-ACTIVATED RECEPTOR2 BY HAT.
4. EFFECT OF HAT ON FIBROBLASTS : IT WAS SHOWN THAT HAT ENHACES GROWTH OF BOTH LUNG AND BRONCHIAL FIBROBLASTS, AND ALSO ENHACES PRODUCTION OF TGF-β1 BY THESE CELLS.
5. CONCLUSION : IT IS POSTULATED THAT HAT IS BIOSYNTHESIZED IN AIRWAY EPITHELIAL CELLS, AND IS RELATED TO BIOLOGICAL DEFENCE MECHANISM OF AIRWAY MUCOSAL MEMBRANE, FOR INSTANCE, HAT IS THOUGHT TO BE RELATED TO BREACKDOWN AND REGENERATION OF AIRWAY MUCOUS MEMBRANE VIA PROCESS OF ACTIVATION OF PROUROKINASE, ACTIVATION OF PLAMINOGEN, ACTIVATION OF METAL PROTEASE SUCH AS COLLAGENASE, AND VIA ENHANCEMENT OF GROWTH OF FIBROBLASTS.HOWEVER, IT IS ALSO POSTULATED THAT HAT IS RELATED TO AMPLIFICATION OF REMODELING OF AIRWAY TISSUES IN CRONIC INFLAMATORY DISEASES WHERE OVERPRODUCTION OF HAT OCCURS.
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