| Project/Area Number |
15390259
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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 | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
FUKUCHI Yoshinosuke Juntendo University, School of Medicine, Respiratory Medicine, Professor, 医学部, 教授 (80010156)
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| Co-Investigator(Kenkyū-buntansha) |
SEYAMA Kuniaki Juntendo University, School of Medicine, Respiratory Medicine, Lecturer, 医学部, 講師 (10226681)
TAKAHASHI Kazuhisa Juntendo University, School of Medicine, Respiratory Medicine, Associate Professor, 医学部, 助教授 (80245711)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2003: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | COPD / Emphysema / Airway Inflammation / Cigarette smoke exposure / Protein modification / Aging / SMP30 / Senescence-accelerated mouse / 炎症性サイトカイン / 慢性喫煙曝露 / ニトロチロシン / 粘液細胞 |
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| Research Abstract |
Aging and smoking are considered as major contributing factors for the development of pulmonary emphysema and airway inflammation. We utilized two mouse strains carrying intrinsic aging factor(s), senescence-accelerated mice (SAM) P1 strain and senescence marker protein-30 (SMP30) knockout (SMP30Y/-) mice. SMP30 is a multifunctional protein providing protection to cellular functions from age-associated deterioration. Both SAMP1 and SMP30Y/- mice are known as a model for senile lung since they have lungs with age-related airspace enlargement and no apparent parenchymal destruction. We evaluated in both strains cigarette smoke induced airway inflammation, emphysema, macromolecule modification by oxidative stress, and aging-related genes in the lungs. Although mice were exposed to cigarette smoke for 8 weeks, histopathological examinations did not detect any significant airway inflammation and remodeling as compared with control strains (SAMR1 and SMP30Y/+, respectively) while they did developed smoke-induced emphysema. In the lungs of SMP30Y/- mice, protein carbonyls tended to increase with aging and significantly higher than the age-matched SMP30Y/+ mice. The protein carbonyls, malondialdehyde, total glutathione, and apoptosis of lung cells were significantly increased after 8-week exposure to cigarette smoke in the SMP30Y/- mice. These results suggests that SMP30 plays important roles in regulating oxidative stress associated with aging and smoking in the lungs. In the gene expression profiles in the lungs of SAMP1, down-regulation of heat shock protein 68 gene as well as up-regulation of I1-1β and CYP2C39 genes were detected and may deserve for future investigation about their role in smoke-induce lung inflammation.
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