| Project/Area Number |
14370215
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | HOKKAIDO UNIVERSITY |
|---|
Principal Investigator |
FUJII Satoshi Hokkaido University Hospital, Lecturer, 病院, 講師 (90291228)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ONOE Kazunori Institute for Genetic Medicine, Professor, 遺伝子病制御研究所, 教授 (40002117)
IWABUCHI Kazuya Institute for Genetic Medicine, Associate Professor, 遺伝子病制御研究所, 助教授 (20184898)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥7,900,000 (Direct Cost: ¥7,900,000)
|
|---|
| Keywords | atherosclerosis / bone marrow derived cells / lymphocyte / NKT cells / mouse / CD1d molecule / gene / cytokine |
|---|
| Research Abstract |
The potential role of CD1d-restricted natural killer T (NKT) cells in the development of atherosclerosis was investigated. When fed an atherogenic diet (AD), NKT cell-deficient CD1d^<-/-> mice had significantly smaller atherosclerotic lesions than AD-fed C57BL/6 (WT) mice. As compared with chow-fed WT mice, administration of the NKT cell ligand α-galactosylceramide (α-GalCer) to AD-fed WT mice resulted in a T helper 1 (Th1)-shifted cytokine response. In addition, repeated injection of α-GalCer or the related glycolipid OCH to apolipoprotein E knockout (apoE^<-7->) mice during the early phase of atherosclerosis significantly enlarged the lesion areas compared to mice injected with vehicle control. However, administration of α-GalCer to apoE^<-/-> mice at the late phase of the disease process (with already established atherosclerotic lesions) exerted no significant influence on the lesion area, but considerably decreased the collagen content. Development of atherosclerosis in either AD-fed WT or apoE^<-/-> mice was associated with the presence of Vα14Jα18 transcripts in the atherosclerotic arterial walls, indicating that NKT cells were recruited to these lesions. Thioglycolate-elicited macrophages pursed with oxidized low-density lipoproteins expressed enhanced CD1d levels and induced NKT cells to produce interferon-γ, a potentially pro-atherogenic Th1 cytokine. Collectively, we conclude that NKT cells are pro-atherogenic in mice.
|
