| Project/Area Number |
09671905
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
UDAGAWA Nobuyuki (1998) Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (70245801)
宇田川 信之 (1997) 昭和大学, 歯学部, 講師 (20138382)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
JIMI Eijiro Showa University, School of Dentistry, Assistant, 歯学部, 助手 (40276598)
TAKAHASHI Naoyuki Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (90119222)
SUDA Tatsuo Showa University, School of Dentistry, Professor, 歯学部, 教授 (90014034)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | Osteoclast / Osteoblast / Bone resorption / Interleukin 18 / Interferon gamma / GM-CSF / T-lymphocyte / Gene targetting mouse |
|---|
| Research Abstract |
IL-18 inhibits osteoclast (CCL) formation in vitro independent of IFN-gamma production, and this was abolished by the addition of neutralizing antibodies to GM-CSF.We now establish that IL-18 was unable to inhibit CCL formation in cocultures using GM-CSF-deficient mice (GM-CSF-/-). Reciprocal cocultures using either wild-type osteoblasts with GM-CSF -/- spleen cells or GM-CSF -/- osteoblasts with wild-type spleen cells were examined. Wild-type spleen cells were required to elicit a response to IL-18 indicating that cells of splenic origin were the IL-18 target. As T cells comprise a large proportion of the spleen cell population, the role of T cells in osteoclastogenesis was examined. Total T cells were removed and repleted in various combinations. Addition of wild-type T cells to a GM-CSF -/- coculture restored IL-18 inhibition of osteoclastogenesis. Major subsets of T cells, 0D4 and CD8+^+, were also individually depleted. Addition of either CD4^+ or CD8^+ wild-type T cells restored IL-18 action in a GM-CSF -/- background, while IL-18 was ineffective when either CD4^+ or CD8^+ GM-CSF -/- T cells were added to a wild-type coculture. These results highlight the involvement of T cells in IL-18-induced CCL inhibition and provide evidence for a new CCL inhibitory pathway whereby IL-18 inhibits CCL formation due to action upon T cells promoting the release of GM-CSF, which in turn acts upon CCL precursors.
|
