2002 Fiscal Year Final Research Report Summary
Enhancement of tumoricidal activity of microglial cell via CD40-CD40 ligand interaction
| Project/Area Number |
13470288
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | NIIGATA UNIVERSITY |
|---|
Principal Investigator |
MORI Hiroshi NIIGATA UNIVERSITY Brain Research Institute Lecturer, 脳研究所, 講師 (70291359)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAWADA Makoto FUJITA HEALTH UNIVERSITY Institute for Comprehensive Medical Science Professor, 総合医科学研究所, 教授 (10187297)
TANAKA Ryuichi Brain Research Institute Professor, 脳研究所, 教授 (30018816)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | microglia / glioma / CD40 / IL-12 / TNF-α / NO |
|---|
| Research Abstract |
Purpuse) It has been reported that CD40-CD40 ligand (CD40L) interaction plays key role for cell mediated immunity on microglial cell as macropharge and dendritic cell. So we examined whether antitumor activity of microglial cell could be enhanced via CD40 induced microglial cell cocultured with CD40L transfected 203 glioma cell lines.
Result) Microglial clone derived form neoborn mouse induced CD40 by combined stimulation of LPS and Interferon (IFN)-g. The following stimulation of soluble CD 40 ligand enhanced TNF-a and NO production of microglia. The supernatants from stimulated microglia via CD 40 ligation mediated killing effect against CD40 transfected 203 glioma cell line as compared to that of the stimulation by LPS, IFN-g, or LPS and IFN-g. Individually applied during CD40 ligation, anti CD40 ligand, antagonists TNF-a, or L-MNNA, or as pairs (anti TNF-a and L-MNNA) inhibited killing activity of the supernatants from stimulated microglia. This indicate that a mixture of the TNF-a and NO, or TNF-a, NO, and other factor(s) mediated significant apoptosis in tumor cell. These findings demonstrate that microglial cells induce apoptosis in tumor cells by at least two of these cytotoxic factors via CD40 engagement.
|
