Comprehensive toxioological assessment of fibrous particles by differential gene expression.
Project/Area Number |
11680563
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
環境影響評価(含放射線生物学)
|
Research Institution | National Institute for Environmental Studies |
Principal Investigator |
HIRANO Seishiro Natl. Inst. Environ. Studies, Independent Senior Research Scientist, 地域環境研究グループ, 主任研究官 (20150162)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | Titanium oxide / Alveolar macrophage / Differential-display / Phagocytosis / krox20 / egr-2 / Northern hybridization / PCR / F ibrous particle / アスベスト / 浮遊粒子状物質 / 肺胞マイクロファージ / デイファレンシャル-デイスプレイ / Krox-20 / ノーザンハイブリダイゼーション |
Research Abstract |
The present study was designed to study differences in biological responses of alveolar macrophages between phagocytosis of he spherical and fibrous particles. Although titanium dioxide is thought to be biologidlay inert, the cytotoxicity of fibrous titanium dioxide (FTiO2) was much higher than spherical TiO2 (STiO2). Differential display and the following Northern blot analysis indicated that transcription of krox2O/egr-2 gene was slightly and greatly upregulated in S and F-TiO2-exposed alveolar macrophages, repectively. The mRNA level of krox20/egr-2 ineased up to 8 hr, when alveolar macrophages were exposed to FTiO2. Quite interestingly the krox20/egr-2 mRNA level was transiently increased, when alveolar macrophages were plated into the culture dish. The analysis with 5' rapid amplification of cDNA ends (5'TACE) suggested that there is a heterogeneity in the upstream region of this gene (Krox20/egr-2 and krox20H1 ; acassion numbers AB032120 and AB032419, respectively). The PCR analysis with specific primers for krox-20/egr-2 and krox20H1 indicated that both genes were almost equally upregulated following either adhesion to the plastic dish or phagocytosis of FTiO2. Picetannol, a Syk kinase inhibitor, completely inhibited the krox20/egr-2 gene expression. These results suggest that tyrosine phosphorylation is implicated in adhesion and phagocytosis of alveolar macrophages, and the expression of krox20/egr-2 may reflect interaction of alveolar macrophages with foreign substances.
|
Report
(3 results)
Research Products
(9 results)