2001 Fiscal Year Final Research Report Summary
The relationship between the desease susceptibility and the regulation of gene expression in the transformation of fibroblast
| Project/Area Number |
11670574
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
TSUKINO Mitsuhiro Kyoto University, Medicine, Assistant Professor, 医学研究科, 助手 (40293956)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAGAI Sonoko Kyoto University, Medicine, Professor, 医学研究科, 助教授 (30217955)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | endogenous steroid / proteinase / smoking |
|---|
| 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.
|
