Source:http://linkedlifedata.com/resource/pubmed/id/17404262
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2007-4-3
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| pubmed:abstractText |
The type IIb heat-labile enterotoxin of Escherichia coli (LT-IIb) and its nontoxic pentameric B subunit (LT-IIb-B(5)) display different immunomodulatory activities, the mechanisms of which are poorly understood. We investigated mechanisms whereby the absence of the catalytically active A subunit from LT-IIb-B(5) renders this molecule immunostimulatory through TLR2. LT-IIb-B(5), but not LT-IIb, induced TLR2-mediated NF-kappaB activation and TNF-alpha production. These LT-IIb-B(5) activities were antagonized by LT-IIb; however, inhibitors of adenylate cyclase or protein kinase A reversed this antagonism. The LT-IIb antagonistic effect is thus likely dependent upon the catalytic activity of its A subunit, which causes elevation of intracellular cAMP and activates cAMP-dependent protein kinase A. Consistent with this, a membrane-permeable cAMP analog and a cAMP-elevating agonist, but not catalytically defective point mutants of LT-IIb, mimicked the antagonistic action of wild-type LT-IIb. The mutants moreover displayed increased proinflammatory activity compared with wild-type LT-IIb. Additional mechanisms for the divergent effects on TLR2 activation by LT-IIb and LT-IIb-B(5) were suggested by findings that the latter was significantly stronger in inducing lipid raft recruitment of TLR2 and interacting with this receptor. The selective use of TLR2 by LT-IIb-B(5) was confirmed in an assay for IL-10, which is inducible by both LT-IIb and LT-IIb-B(5) at comparable levels; TLR2-deficient macrophages failed to induce IL-10 in response to LT-IIb-B(5) but not in response to LT-IIb. These differential immunomodulatory effects by LT-IIb and LT-IIb-B(5) have important implications for adjuvant development and, furthermore, suggest that enterotoxic E. coli may suppress TLR-mediated innate immunity through the action of the enterotoxin A subunit.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Enterotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Escherichia coli Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/TLR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/heat-labile enterotoxin, E coli
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
178
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4811-9
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:17404262-Animals,
pubmed-meshheading:17404262-Bacterial Toxins,
pubmed-meshheading:17404262-CHO Cells,
pubmed-meshheading:17404262-Cells, Cultured,
pubmed-meshheading:17404262-Cricetinae,
pubmed-meshheading:17404262-Cricetulus,
pubmed-meshheading:17404262-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:17404262-Cytokines,
pubmed-meshheading:17404262-Enterotoxins,
pubmed-meshheading:17404262-Escherichia coli Proteins,
pubmed-meshheading:17404262-Humans,
pubmed-meshheading:17404262-Immunity, Innate,
pubmed-meshheading:17404262-Inflammation,
pubmed-meshheading:17404262-NF-kappa B,
pubmed-meshheading:17404262-Protein Subunits,
pubmed-meshheading:17404262-Signal Transduction,
pubmed-meshheading:17404262-Toll-Like Receptor 2,
pubmed-meshheading:17404262-Tumor Necrosis Factor-alpha
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| pubmed:year |
2007
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| pubmed:articleTitle |
The A subunit of type IIb enterotoxin (LT-IIb) suppresses the proinflammatory potential of the B subunit and its ability to recruit and interact with TLR2.
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| pubmed:affiliation |
Center for Oral Health and Systemic Disease, Department of Periodontics, University of Louisville Health Sciences Center, Louisville, KY 40292, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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