1998 Fiscal Year Final Research Report Summary
Proteinase and Proteinase inhibitor production of Alveolar cells and the effects of cigarette smoking
| Project/Area Number |
09670610
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
NISHIMURA Koichi Kyoto University, Respiratory Medicine, Lecturer, 医学研究科, 講師 (80243096)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Sonoko Kyoto University, Respiratory Medicine, Associate Professor, 医学研究科, 助教授 (30217955)
MIO Tadashi Kyoto University, Respiratory Medicine, Assistant Professor, 医学研究科, 助手 (90243097)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Alveolar cells / Tissue Inhibitors of Metalloproteinase-3 / Matrix Metalloproteinase-3 / Cigarette Smoking / apoptosis / Oxidant |
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| Research Abstract |
We examined mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in alveolar cells and cytotoxic effects of cigarette smoke to the alveolar cells.
#1 The mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in the cell line (A549) and in the primary culture of normal adult human type II pneumocytes were examined using reverse transcription-competitive polymerase chain reaction. The TIMP-3 and MMP-3 mRNA expressions were constitutively present in both of the cells. Interleukin-1β(IL-1β) and transforming growth factor-β1(TGF-β1) increased both MMP-3 and TIMP-3 expressions in time- and concentration-dependent manners. However, IL-1β mainly augmented MMP-3 expression, while TGF-β1 mainly augmented TIMP-3 expression. These data may indicate that IL-1β enhances the matrix degradation and TGF-β1 suppresses it by regulating the balance between MMP-3 and TIMP-3.
#2 Cigarette smoke extract (CSE) caused apoptosis at the coocentrations of 5% or less and necrosis at 10% or more. The cytotoxic activity were mainly present in volatile phase of CSE. Two volatile factcrs in cigarette smoke, acrolein and hydrogen peroxide caused cell death. N-acetylcysteine, a scavenger of oxidants and aldehydes, and aldehyde dehydrogenase completely inhibited the apoptosis. CSE and acrolein increased intracellular oxidant activity, which assessed using dichlorofluorescein derivative. In conclusion, apoptosis of alveolar epithelial cells is one of the mochanisms of lung injury induced by cigarette smoking. This cytotoxic effect may be attributed by an interaction of aldehyde and oxidants which were present in CSE or for med in the cells exposed to CSE.
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