| RRC ID |
41619
|
| 著者 |
Dirgahayu P, Fukumoto S, Miura K, Hirai K.
|
| タイトル |
Excretory/secretory products from plerocercoids of Spirometra erinaceieuropaei suppress the TNF-alpha gene expression by reducing phosphorylation of ERK1/2 and p38 MAPK in macrophages.
|
| ジャーナル |
Int J Parasitol
|
| Abstract |
We previously reported that excretory/secretory products from plerocercoids of Spirometra erinaceieuropaei suppress gene expression and production of tumour necrosis factor-alpha in murine macrophages stimulated with lipopolysaccharide. The present study investigated the suppressive mechanisms of tumour necrosis factor-alpha mRNA by excretory/secretory products in lipopolysaccharide-stimulated murine macrophages. Electrophoretic mobility shift assay and supershift assay revealed that neither nuclear translocation of nuclear factor-kappa B nor conformation of the p50/p65 nuclear factor-kappa B subunits was affected by the treatment of excretory/secretory products in lipopolysaccharide-stimulated macrophages. Inhibition of extracellular signal-regulated protein kinase 1/2 with PD98059 or p38 mitogen-activated protein kinase with SB203580 partially reduced tumour necrosis factor-alpha mRNA expression, and a combination of the two inhibitors additionally suppressed the level of tumour necrosis factor-alpha mRNA, revealing that both pathways are crucial for full induction of the gene. Northern blot analysis showed that excretory/secretory products additionally suppressed tumour necrosis factor-alpha mRNA expression in cells treated with PD98059 or SB208530 and, in turn, we found that excretory/secretory products reduced phosphorylation of extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinase in lipopolysaccharide-stimulated macrophages by Western blot analysis. This is the first report demonstrating that excretory/secretory products from parasites suppress tumour necrosis factor-alpha mRNA expression by reducing phosphorylation of extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinase without any effect on nuclear factor-kappa B activity in macrophages stimulated with lipopolysaccharide. We hypothesise that excretory/secretory products may enable this parasite to survive within the host.
|
| 巻・号 |
32(9)
|
| ページ |
1155-62
|
| 公開日 |
2002-8-1
|
| DOI |
10.1016/s0020-7519(02)00090-5
|
| PII |
S0020751902000905
|
| PMID |
12117498
|
| MeSH |
Animals
Biological Factors / pharmacology*
Blotting, Northern
Gene Expression Regulation / drug effects*
Lipopolysaccharides / pharmacology
Macrophage Activation / drug effects
Macrophages / drug effects*
Macrophages / enzymology
Macrophages / metabolism*
Mitogen-Activated Protein Kinases / genetics
Mitogen-Activated Protein Kinases / metabolism*
Phosphorylation / drug effects
RNA Processing, Post-Transcriptional
RNA, Messenger / genetics
RNA, Messenger / metabolism
Spirometra / metabolism*
Spirometra / pathogenicity
Tumor Necrosis Factor-alpha / biosynthesis
Tumor Necrosis Factor-alpha / genetics*
p38 Mitogen-Activated Protein Kinases
|
| IF |
3.53
|
| 引用数 |
17
|
|
WOS 分野
|
PARASITOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
