Document Detail


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.
MedLine Citation:
PMID:  12117498     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Paramasari Dirgahayu; Soji Fukumoto; Kazutoyo Miura; Kazumitsu Hirai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal for parasitology     Volume:  32     ISSN:  0020-7519     ISO Abbreviation:  Int. J. Parasitol.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-07-15     Completed Date:  2002-11-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0314024     Medline TA:  Int J Parasitol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1155-62     Citation Subset:  IM    
Affiliation:
Department of Molecular Medical Zoology, Faculty of Medicine, Tottori University, 86 Nishi-cho, 683-8503 Yonago, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Factors / pharmacology*
Blotting, Northern
Gene Expression Regulation / drug effects*
Lipopolysaccharides / pharmacology
Macrophage Activation / drug effects
Macrophages / drug effects*,  enzymology,  metabolism*
Mitogen-Activated Protein Kinases / genetics,  metabolism*
Phosphorylation / drug effects
RNA Processing, Post-Transcriptional
RNA, Messenger / genetics,  metabolism
Spirometra / metabolism*,  pathogenicity
Tumor Necrosis Factor-alpha / biosynthesis,  genetics*
p38 Mitogen-Activated Protein Kinases
Chemical
Reg. No./Substance:
0/Biological Factors; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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