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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2004-5-4
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pubmed:abstractText |
Toll-like receptor 4 (TLR4)-mediated responses, which are induced by the lipid A portion of lipopolysaccharide, are important for host defense against Salmonellae infection. A variety of different data indicate that the acylation state of lipid A can alter TLR4-mediated responses. The S. typhimurium virulence gene product PhoP/PhoQ signals the presence of host microenvironments to regulate the expression of a lipid A 3-O-deacylase, PagL, and a lipid A palmitoyltransferase, PagP. We now demonstrate that 3-O-deacylation and palmitoylation of lipid A decreases its ability to induce TLR4-mediated signaling. Deacylated lipid A, deacylated and palmitoylated lipid A, palmitoylated lipid A, and unmodified lipid A species were purified from Escherichia coli heterologously expressing PagL and/or PagP. The purified lipid A preparations showed spectra of a single lipid A species on mass spectrometry and gave a single band on thin layer chromatography. The activity of purified lipid A species was examined using human and mouse cell lines that express recombinant human TLR4. Compared with unmodified lipid A, the modified lipid A species are 30-100-fold less active in the ability to induce NF-kappaB-dependent reporter activation. These results suggest that the lipid A modifications reduce TLR4-signaling as part of Salmonellae adaptation to host environments.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxylic Ester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Escherichia coli Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipid A,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PagL protein, Salmonella typhimurium,
http://linkedlifedata.com/resource/pubmed/chemical/PagP protein, E coli,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20044-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15014080-Acyltransferases,
pubmed-meshheading:15014080-Animals,
pubmed-meshheading:15014080-Bacterial Proteins,
pubmed-meshheading:15014080-Carboxylic Ester Hydrolases,
pubmed-meshheading:15014080-Chromatography, Thin Layer,
pubmed-meshheading:15014080-Dose-Response Relationship, Drug,
pubmed-meshheading:15014080-Escherichia coli,
pubmed-meshheading:15014080-Escherichia coli Proteins,
pubmed-meshheading:15014080-Humans,
pubmed-meshheading:15014080-Lipid A,
pubmed-meshheading:15014080-Mass Spectrometry,
pubmed-meshheading:15014080-Membrane Glycoproteins,
pubmed-meshheading:15014080-Mice,
pubmed-meshheading:15014080-Models, Chemical,
pubmed-meshheading:15014080-NF-kappa B,
pubmed-meshheading:15014080-Plasmids,
pubmed-meshheading:15014080-Receptors, Cell Surface,
pubmed-meshheading:15014080-Recombinant Proteins,
pubmed-meshheading:15014080-Signal Transduction,
pubmed-meshheading:15014080-Toll-Like Receptor 4,
pubmed-meshheading:15014080-Toll-Like Receptors
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pubmed:year |
2004
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pubmed:articleTitle |
3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4.
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pubmed:affiliation |
Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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