Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
2005-9-21
pubmed:abstractText
Commensal and enteroinvasive microbes in the human gut release bacterial flagellin, a specific microbial ligand of Toll-like receptor 5 (TLR5). However, the pathophysiological role of bacterial flagellin in gastrointestinal inflammation has not been determined. Here we evaluated the role of bacterial flagellin using native human colonic mucosa and the mouse colitis model of dextran sulfate sodium (DSS). We demonstrate that, in intact human colonic mucosa, the flagellin/TLR5 response occurs only after exposure to the basolateral, not the apical, surface, implying a basolaterally polarized TLR5 response in human colonic mucosa. In this context, flagellin exposure to injured colonic mucosa due to DSS administration in mice resulted in a TLR5-associated response evaluated by in vivo activation of mitogen-activated protein kinase/extracellular signal-related kinase 1/2 (MEK1/2) and elevated IL-6, TNF-alpha, and keratinocyte-derived chemokine production, whereas intact colonic mucosa did not respond to flagellin. Moreover, flagellin exposure to injured mouse colon in vivo, but not to intact colon, also significantly aggravated colonic inflammation, increased mouse mortality, and enhanced histopathological damage in the colonic mucosa. However, the TLR2-specific agonist, peptidoglycan or lipoteichoic acid, did not cause an inflammatory response in intact or DSS-injured mouse colon. Furthermore, intracolonic flagellin administration in mice causes severe apoptosis in colonic epithelium disrupted by DSS administration. These data suggest that intracolonic flagellin via TLR5 engagement is able to elicit inflammatory responses in disrupted colon, whereas the normal colon is not responsive to bacterial flagellin. These results demonstrate that bacterial flagellin plays an important role in the development and progress of colitis.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-10480018, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-10930370, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-10952994, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-11083826, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-11157169, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-11485733, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-11489966, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-11781279, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-11790539, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-11821427, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12055606, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12427784, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12474223, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12495726, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12544192, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12686553, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12691258, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12900270, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-12970149, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-14634022, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-14699484, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15057745, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15069060, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15124021, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15153511, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15260992, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15302888, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15340409, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15630445, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15632166, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-15634902, http://linkedlifedata.com/resource/pubmed/commentcorrection/16157881-9851930
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, http://linkedlifedata.com/resource/pubmed/chemical/Flagellin, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Map2k1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Map2k2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptidoglycan, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/TLR2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/TLR5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Teichoic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2, http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 5, http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/lipoteichoic acid
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13610-5
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16157881-Humans, pubmed-meshheading:16157881-Animals, pubmed-meshheading:16157881-Mice, pubmed-meshheading:16157881-Colon, pubmed-meshheading:16157881-Colitis, pubmed-meshheading:16157881-Inflammation, pubmed-meshheading:16157881-Intestinal Mucosa, pubmed-meshheading:16157881-Lipopolysaccharides, pubmed-meshheading:16157881-Male, pubmed-meshheading:16157881-Tissue Culture Techniques, pubmed-meshheading:16157881-Receptors, Cell Surface, pubmed-meshheading:16157881-Teichoic Acids, pubmed-meshheading:16157881-Peptidoglycan, pubmed-meshheading:16157881-Signal Transduction, pubmed-meshheading:16157881-Flagellin, pubmed-meshheading:16157881-Apoptosis, pubmed-meshheading:16157881-Membrane Glycoproteins, pubmed-meshheading:16157881-Keratinocytes, pubmed-meshheading:16157881-Tumor Necrosis Factor-alpha
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