Document Detail


The type III pseudomonal exotoxin U activates the c-Jun NH2-terminal kinase pathway and increases human epithelial interleukin-8 production.
MedLine Citation:
PMID:  16790784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microbial interactions with host cell signaling pathways are key determinants of the host cell response to infection. Many toxins secreted by bacterial type III secretion systems either stimulate or inhibit the host inflammatory response. We investigated the role of type III secreted toxins of the lung pathogen Pseudomonas aeruginosa in the inflammatory response of human respiratory epithelial cells to infection. Using bacteria with specific gene deletions, we found that interleukin-8 production by these cells was almost entirely dependent on bacterial type III secretion of exotoxin U (ExoU), a phospholipase, although other bacterial factors are involved. ExoU activated the c-Jun NH(2)-terminal kinase pathway, stimulating the phosphorylation and activation of mitogen-activated kinase kinase 4, c-Jun NH(2)-terminal kinase, and c-Jun. This in turn increased levels of transcriptionally competent activator protein-1. Although this pathway was dependent on the lipase activity of ExoU, it was independent of cell death. Activation of mitogen-activated kinase signaling by ExoU in this fashion is a novel mechanism by which a bacterial product can initiate a host inflammatory response, and it may result in increased epithelial permeability and bacterial spread.
Authors:
Alayne Cuzick; Fiona R Stirling; Susan L Lindsay; Thomas J Evans
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Infection and immunity     Volume:  74     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-22     Completed Date:  2006-08-24     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4104-13     Citation Subset:  IM    
Affiliation:
Division of Immunology, Infection and Inflammation, University of Glasgow, Western Infirmary, Glasgow G11 6NT, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Epithelial Cells / enzymology,  immunology,  metabolism*
Exotoxins / physiology*
Humans
Interleukin-8 / biosynthesis*
JNK Mitogen-Activated Protein Kinases / physiology*
MAP Kinase Signaling System / immunology*
Pseudomonas aeruginosa / genetics,  pathogenicity,  physiology*
Up-Regulation* / immunology
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Exotoxins; 0/Interleukin-8; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases
Comments/Corrections

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