| Project/Area Number |
09672210
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
OHUCHI Kazuo Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20006357)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | platelet-activating factor / tumor necrosis factor-alpha / thapsigargin / indomethacin / macrophage / prostaglandin E2 / SK & F 98625 / E6123 / L-652,731 / prostaglandin E_2 / SK&F98625 |
|---|
| Research Abstract |
Stimulation of rat peritoneal macrophages by thapsigargin (46.1 nM) increased levels of tumor necrosis factor-a and prostaglandin E2 in the conditioned medium.
Platelet-activating factor was not detected in the conditioned medium, but the level of cell-associated platelet-activating factor was increased transiently by thapsigargin.
The receptor antagonists of platelet-activating factor such as E6123, L-652,731and CV-6209 inhibited thapsigargin-induced production of tumor necrosis factor-alpha. The cyclooxygenase inhibitor indomethacin inhibited prostaglandin E2production, and further enhanced thapsigargin-induced tumor necrosis factor-alphaproduction in parallel with further increase in cell-associated platelet-activating factor production.
The enhancement of tumor necrosis factor-a production induced by thapsigarginplus indomethacin was also inhibited by E6123, L-652,731 and CV-6209.
However, exogenously added platelet-activating factor up to 100 nM did not stimulate production of tumor necrosis factor-a.
The level of tumor necrosis factor-alpha mRNA was increased by thapsigargin, but was lowered by the platelet-activating factor antagonist E6123, suggesting that the inhibition of tumor necrosis factor-a production by the platelet-activating factor antagonist is induced at the level of mRNA for tumor necrosis factor-a.
These findings suggested that concurrently produced cell-associated platelet-activating factor up-regulates production of tumor necrosis factor-a by acting as an intracellular signaling molecule, and the antagonists of platelet-activating factor might penetrate into the cells and antagonize the action of intracellular platelet-activating factor.
|
