Remodeling and mucin expression by ultrafine carbon particles in airway epithelium
| Project/Area Number |
16590763
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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 | Tokyo Women's Medical University |
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Principal Investigator |
TAMAOKI Jun Tokyo Women's Medical Univ., Medicine, Professor, 医学部, 教授 (60147395)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Airway epithelium / Remodeling / Epidermal growth factor / MUC gene / Carbon particle / Goblet cell / Mucin secretion / Asthma / 杯細胞 / 大気汚染 / カーボンブラック / ムチン / 上皮成長因子受容体 / アダプター分子 / 炎症性サイトカイン |
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| Research Abstract |
Exposure to ambient ultrafine particles induces airway inflammatory reactions and tissue remodeling. In this experiment, to determine whether ultrafine carbon black (ufCB) affects proliferation of airway epithelium and, if so, what the mechanism of action is, we studied human primary bronchial epithelial cell cultures. Incubation of cells in the serum-free medium with ufCB increased incorporations of [^3H]-thymidine and [^3H]-leucine into cells in a time- and dose-dependent manner. This effect was attenuated by a free radical scavenger and a NADH/NADPH oxidase inhibitor, and completely inhibited by pretreatment with the epidermal growth factor receptor (EGF-R) tyrosine kinase inhibitors AG1478 and BIBX1382, and the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059. Transfection of a dominant negative mutant of H-Ras likewise abolished the effect ufCB. Stimulation with ufCB also induced processing of membrane anchored pro-heparin-binding (HB)-EGF, release of soluble HB-EGF into the medium, association of phosphorylated EGF-R and Shc with glutathione-S-transferase-Grb2 fusion protein, and phosphorylation of extracellular signal-regulated kinase (ERK). Pretreatment with each AG1478, [Glu^<52>]Diphtheria toxin, a specific inhibitor of HB-EGF, and neutralizing HB-EGF antibody inhibited ufCB-induced ERK activation. These results suggest that ufCB causes oxidative stress-mediated proliferation of airway epithelium, involving processing of HB-EGF and the concomitant activation of EGF-R and ERK cascade.
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Report
(3 results)
Research Products
(18 results)
