| Project/Area Number |
11670574
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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 |
TSUKINO Mitsuhiro Kyoto University, Medicine, Assistant Professor, 医学研究科, 助手 (40293956)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Sonoko Kyoto University, Medicine, Professor, 医学研究科, 助教授 (30217955)
西村 浩一 京都大学, 医学研究科, 講師 (80243096)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | endogenous steroid / proteinase / smoking / サイトカイン / 成長因子 / RT-PCR / 間質性肺炎 / 線維化 / 線維芽細胞 / 形質変換機構 / α-SM actin / glucocorticoid / 家族集積 / 疾患感受性 |
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| Research Abstract |
[Objective]
To evaluate the relationship among the endogenous steroid, the regulation of steroid sulfatase (STS) expression, and cigarettesmoking induced imbalance of proteinase/antiproteinase in the alveolar epithelium derived cell line and alveolar macrophages from patients with inflammatory pulmonary diseases.
[Method]
We examined the levels of STS expression in alveolar macrophages from BALF of inflammatory pulmonary diseases such as idiopatiiic pulmonary fibrosis and sarcoidosis, and normal healthy controls using RT-competitive PCR. We also evaluated the effect of smoking and glucocorticosteroids on the expression of MMP-3 and TIMP-3 in A549 cell line using RT-competitive PGR. We standardized the amount of competitive PCR products by the competition with mutant cDNA comparing housekeeping gene, GADPH mRNA.
[Results]
Alveolar macrophage constitutively expressed STS. However, as for the level of the expression of STS, there is no significant difference between normal never smoking controls and smoking subjects. Neither we found the upregulation of the expression of STS in inflammatory disease patients. The addition of the smoke extract upregulated the expression of MMP-3 and TIMP-3 in A549 cell line, however, dexamethasone and dehydroepiandrosterone (DHEA) did not inhibit this upregulation.
[Discussion]
Although Glucocorticoid and DHEA are shown to possess the activity of antibxidant and anti-inflammation, smoking related imbalance of proteinase/antiproteinase were not affected by those steroids, suggesting other mechanism than oxidant may play be a important factor of smoking related hing injury.
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