| Entamoeba histolytica cysteine proteinases with interleukin-1 beta converting enzyme (ICE) activity cause intestinal inflammation and tissue damage in amoebiasis. | |
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MedLine Citation:
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PMID: 10931347 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The protozoan parasite Entamoeba histolytica causes intestinal inflammation and ulceration. Amoebic trophozoites activate the transcription factor NF-kappa B in human intestinal epithelial cells, initiating an inflammatory response programme with resultant damage to the intestinal tissue. Amoebic cysteine proteinases have been proposed as important virulence factors for amoebiasis. To test the role of amoebic cysteine proteinases in the pathogenesis of amoebic colitis, human intestinal xenografts in SCID mice were infected with E. histolytica trophozoites expressing an antisense message to ehcp5. The cysteine proteinase-deficient amoeba failed to induce intestinal epithelial cell production of the inflammatory cytokines interleukin (IL)-1B and IL-8, and caused significantly less gut inflammation and damage to the intestinal permeability barrier. The critical role of amoebic cysteine proteinases in human gut inflammation and tissue damage may be explained by our discovery that amoebic cysteine proteinases possess IL-1B converting enzyme (ICE) activity. This ICE activity could contribute to intestinal inflammation by activating human pIL-1B released by damaged intestinal cells. These results demonstrate for the first time that amoebic cysteine proteinases are a key virulence factor in amoebic colitis, and provide a novel mechanism for their activity. |
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Authors:
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Z Zhang; L Wang; K B Seydel; E Li; S Ankri; D Mirelman; S L Stanley |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular microbiology Volume: 37 ISSN: 0950-382X ISO Abbreviation: Mol. Microbiol. Publication Date: 2000 Aug |
Date Detail:
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Created Date: 2000-09-12 Completed Date: 2000-09-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8712028 Medline TA: Mol Microbiol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 542-8 Citation Subset: IM |
Affiliation:
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Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amebiasis
/
etiology,
genetics,
parasitology*,
pathology* Animals Bacterial Proteins / genetics, metabolism* Caspase 1 / genetics, metabolism* Cysteine Endopeptidases / genetics, metabolism* Entamoeba histolytica / genetics, metabolism* Humans Inflammation / parasitology Intestines / parasitology*, pathology* Mice Mice, SCID Oligonucleotides, Antisense Transplantation, Heterologous |
| Grant Support | |
ID/Acronym/Agency:
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AI01231/AI/NIAID NIH HHS; AI30084/AI/NIAID NIH HHS; DK52574/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Proteins; 0/Oligonucleotides, Antisense; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.36/Caspase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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