2004 Fiscal Year Final Research Report Summary
Analysis of signaling molecules in the pathogenesis of COPD and bronchial asthma
| Project/Area Number |
14570568
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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 |
Respiratory organ internal medicine
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| Research Institution | Nihon University |
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Principal Investigator |
HASHIMOTO Shu Nihon University, School of Medicine, Assistant Professor, 医学部, 講師 (30159090)
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| Co-Investigator(Kenkyū-buntansha) |
HORIE Takashi Nihon University, School of Medicine, Professor, 医学部, 教授 (60090081)
SHIMIZU Kazufumi Nihon University, School of Medicine, Professor, 医学部, 教授 (50004677)
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| Project Period (FY) |
2002 – 2004
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| Keywords | COPD / bronchial asthma / MAP kinase / ASK1 / airway epithelial cell / oxidative stress |
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| Research Abstract |
Airway epithelial cells(AEC) participate in the production of airway inflammation by expressing various cytokines. Many extracellular stimuli elicit specific biological responses through activation of mitogen-activated protein kinase(MAPK), ERK, p38 MAPK and c-Jun-NH2-terminal kinase(JNK), cascades. Each MAPK is activated by distinct upstream kinase. MEKK1-4, ASK1 and TAK1 were identified as a member of the MAPK kinase kinase(MAPKKK) family that activates SEK1/MKK7-JNK and MKK3/MKK6-p38 MAPK pathways. We have examined the role of MAPK cascades in transcription activation, cytokine expression and cell apoptosis in AEC in response to various stimuli, including cigarette smoking extract(CSE), hydrogen peroxide. In addtion, the role of ASK1 in the induction of AP-1 activation in human airway smooth muscle cells(ASMC). The results shoed that 1)CSE activate ASK1-p38 MAPK to express MMP-9 in AEC, 2)hydrogen peroxide activates ASK1 to induce cell apoptosis via caspase-3,and 3)LTD4 activates ASK1 to induce AP-1 activation in ASMC. These results indicate that ASK1 plays a crucial role in the production of airway inflammation of COPD and bronchial asthma. The analysis of signaling pathway leading to transcription factor activation and cytokine expression, and its regulation may be beneficial in therapeutic strategy of airway inflammation.
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Research Products
(9 results)
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[Journal Article] Interferon-β attenuates bleomycin-induced pulmonary fibrosis by decreasing levels of thrombospondin.2004
Author(s)
Azuma A, Li YJ, Abe S, Usuki J, Matsuda K, Henmi S, Miyauchi Y, Ueda K, Izawa A, Sone S, Hashimoto S, Kudoh S.
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Journal Title
Am J Respir Cell Mol Biol 32
Pages: 93-98
Description
「研究成果報告書概要(欧文)」より
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