2007 Fiscal Year Final Research Report Summary
Clarification of the underlying mechanism of allergic diseases targeting the signal pathways of the involved cytokines
| Project/Area Number |
18604007
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
アレルギー
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| Research Institution | Saga University |
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Principal Investigator |
IZUHARA Kenji Saga University, Saga Medical School, Dept. Biomol Sciences, Professor (00270463)
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| Co-Investigator(Kenkyū-buntansha) |
KANAJI Sachiko Saga University, Saga Medical School, Dept. Biomol Sciences, Assistant Professor (50363429)
OHTA Shoichiro Saga University, Saga Medical School, Dept. Biomol Sciences, Assistant Professor (20346886)
SHIRAISHI Hiroshi Saga University, Saga Medical School, Dept. Biomol Sciences, Assistant Professor (80452837)
NAGAI Hiroichi Gifu Pharmaceutical University, Dept Pharm, Professor (90082974)
INOUE Makoto DNAVEC Corp., ベクター開発室, Director (30373541)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Allergv / Asthma / Gene / Protein / Immunology |
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| Research Abstract |
We found in this study that periostin, an extracellular matrix protein, is a component of fibrosis in bronchial asthma and that pendrin, an anion exchanger, is a mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease (COPD). In the former project, we obtained the following results. (1) Upon stimulation of IL-4/IL-13, lung fibroblasts secreted periostin. (2) Periostin was deposited in the fibrotic legions of asthma. (3) Periostin bound to other matrix proteins such as tenascin-C, fibronectin, and collagen V. These results suggest that periostin is secreted from lung fibroblasts stimulated with IL-4/IL-13 in bronchial asthma and is involved in fibrosis of asthma by binding to other matrix proteins. In the latter project, we obtained the following results. (1) Bronchial epithelial cells cultured by the air-interface method in the presence of IL-13 differentiated into mucus-producing cells and these cell expressed pendrin. (2) Expression of pendrin was up-regulated in lung tissues of bronchial asthma and COPD. (3) Enforced expression of pendrin in airway cells caused mucus production. (4) Enforced expression of pendrin into mouse lungs caused mucus production with infiltration of neutrophils. These results suggest that pendrin is induced in the lung tissues of bronchial asthma and COPD and is involved in mucus production in these diseases. Fibrosis and mucus production are deeply correlated with morbidity and mortality of bronchial asthma and COPD. Therefore, the present results are useful to comprehend the whole molecular mechanism of fibrosis and mucus production in bronchial asthma and COPD and to develop therapeutic reagents against these phenotypes.
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