Project/Area Number |
11670603
|
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 | University of Occupational Environmental Health |
Principal Investigator |
MORIOMOTO Yasuo UOEH, Institute of Industrial Ecological Sciences, ^*Professor, 産業生態科学研究所, 教授 (30258628)
|
Co-Investigator(Kenkyū-buntansha) |
OHGAMI Akira UOEH, Institute of Industrial Ecological Sciences, <@D1*@>D1Research Associate, 産業生態科学研究所, 助手 (40301692)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
|
Keywords | Clara cell / CCSP / Silica / Cigarette |
Research Abstract |
Clara cell secretory protein (CCSP) is thought to play a role as a regulator of inflammatory response. To investigate how CCSP plays a role in lung remodeling induced by exposure to cigarette smoke, we examined gene expression of matrix metalloproteinases (MMPs) and chemokines mRNA in lungs of mice exposed to cigarette smoke. CCSP deficient (CCSP-/-) strain 129 and wild type (WT) strain 129 mice were exposed to cigarette-smoke for 4 hours a day, for 4 weeks. No significant differences were observed in gene expression of MMP-2, MMP-9, IL-10 and MIP-2 mRNA between CCSP-/- and wild type mice exposed to cigarette smoke. This suggests that CCSP is not correlated with cigarette smoke-induced pulmonary response through MMPs and chemokines. We also investigated the function of Clara cells in vivo during exposure to inhaled crystal-line silica by examining pulmonary matrix metalloproteinase (MMP)-2 and MMP-9 mRNA levels in mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg) in a corn oil vehicle. The mice were then exposed to crystalline silica (Min-U-Sil-5 silica, 97.1±9.5 mg/m^2, 6 hours/day, 5 days/week) for up to 2 weeks. Gene expression of both MMP-2 and MMP-9 was significantly more marked in the Clara cell-ablated group than in the group with Clara cells, indicating that Clara cells inhibit MMPs expression. Our findings suggest that Clara cells inhibit pulmonary inflammation induced by crystalline silica via MMPs in vivo.
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