2003 Fiscal Year Final Research Report Summary
Research on a parasite factor suppressing the gene expression of TNF-α and chemokines in macrophages
| Project/Area Number |
13670246
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
寄生虫学(含医用動物学)
|
|---|
| Research Institution | Tottori University |
|---|
Principal Investigator |
FUKUMOTO Soji Tottori University, Department of Microbiology and Pathology, Associate Professor, 医学部, 助教授 (60111126)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HIRAI Kazumitsu Tottori University, Department of Microbiology and Pathology, Professor, 医学部, 教授 (20093940)
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Keywords | Spirometra erinaceieuropaei / Excretory / secretory products / macrophage / IP-10 / chemokine / gene expression / LPS / IFN-γ |
|---|
| Research Abstract |
Excretory/secretory (ES) products from Spirometra erinaceieuropaei plerocercoids suppressed the IP-10 gene expression, but not IRF-1, in macrophages stimulated with LPS or IFN-γ. IP-10 gene in LPS-stimulated macrophages will be induced by IFN-β through the MyD88 independent pathway, and ES products suppressed not only IFN-β gene expression but also IP-10, which was clarified by Northern blot analysis or RT-PCR. ES products suppressed the phosphorylation of STAT-1 Tyr701 in macrophages 3 h after the stimulation with LPS, but did not suppress the phosphorylation in the case of IFN-γ stimulation. The data of gel shift assay showed that the nuclear translocation and DNA binding activity of STAT-1 or ISGF3 did not change in macrophages stimulated with IFN-γ or IFN-β by the addition of ES products. Then, we examined the effects of ES products on the luciferase activities of macrophages transfected with luciferase vector containing -243 promoter or enhancer region of IP-10, which is the minimum response region. ES products suppressed the luciferase activities of macrophages stimulated with LPS and br IFN-γ. These data suggest that the suppressive mechanisms of IP-10 gene expression by ES products did not based on the inhibition of DNA binding activity of transcription factors such as STAT-1 and NF-κB, and originated from the conformation in IP-10 promoter. ES products also suppressed inducible nitric oxide synthase and the nitrite production, but ES products increased the CIITA and MHCII gene expression in the IFN-γ stimulated macrophages.
|
