| Project/Area Number |
10670423
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | KITASATO UNIVERSITY |
|---|
Principal Investigator |
AKAHOSHI Tohru Kitasato Univ.School of Medicine, Department of Internal Medicine, Assistant Professor, 医学部, 講師 (70159325)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANAKA Sumiaki MD, Kitasato Univ.School of Medicine, Department of Internal Medicine, Research Associate, 医学部, 助手 (80265595)
HOSAKA Shigeru MD, Kitasato Univ.School of Medicine, Department of Internal Medicine, Assistant Professor, 医学部, 講師 (80209220)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | rheumatoid arthritis / neutrophils / apoptosis / PGE_2 / 炎症 / 滑膜細胞 |
|---|
| Research Abstract |
Infiltration of neutrophils into the inflamed joints is a characteristic feature of rheumatoid arthritis (RA). Accumulated neutrophils play pivotal roles on destruction of the inflamed joints through the elaboration of inflammatory mediators. Neutrophils are short-lived cells and spontaneously die by apoptosis. A number of factors have been shown to modulate spontaneous neutrophil apoptosis. However, the regulatory mechanisms of neutrophil apoptosis in RA have not been elucidated. We investigated the regulatory roles of synovial cell-derived-factors and various anti-rheumatic drugs on neutophil apoptosis. The results obtained in this study are as following. (1) Pro-inflammatory cytokines (IL-1, TNF-α) produce soluble factor (s) capable of inhibiting spontaneous neutrophil apoptosis. (2) GM-CSF is a major factor for this activity. (3) A novel inhibitory factor for neutrophil apoptosis (MW about 25 Kd) has been found. (4) PGE2 prevented neutrophil apoptosis through the binding to the receptors (EP4 and EP2) on neutrophils. On the other hand, EP3 agonist rapidly promoted unique death of neutrophils resembling to apoptosis. (5) Among the anti-rheumatic drugs examined, sulfasalazine rapidly promoted neutrophil apoptosis and lipophilic gold complex (auranofin) also modulated cellular death. These findings indicate that joint inflammation potentially elongates neutrophil survival by inhibiting apoptosis and the drugs used in the treatment of RA promote neutrophil death by inducing apoptosis.
|
