Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-3-22
pubmed:abstractText
Mucosal epithelial linings function as physical barriers against microbes. In addition, they participate in the first line of host defence by production of a variety of proinflammatory mediators when exposed to microbes and microbial agents. Here, we use a human urinary tract infection model to demonstrate that organ- and cell-specific innate responses induced by lipopolysaccharides (LPS) present on Gram-negative bacteria correlates with the expression of Toll-like receptor 4 (TLR4). The presence of TLR4 on human bladder epithelial cells enables them to rapidly respond to bacterial infections in vitro and in vivo. In contrast, TLR4 is not expressed on human proximal tubule cells isolated from the renal cortex, which may explain the cortical localization of bacteria in pyelonephritis. TLR4-negative renal epithelial cells, A498, are non-responsive to purified LPS, however, they respond to viable bacteria via a mannose-sensitive attachment-mediated pathway. To identify LPS components recognised by bladder epithelial cells, a bacterial lipid A mutant and LPS of different chemotypes were tested. Full interleukin 8 induction required hexa-acylated lipid A and was decreased by between 50% and 70% in the presence of O-antigen. Taken together, we propose that multiple independent pathways, which are organ- and cell-specifically expressed, mediate bacterial recognition and determine the outcome of innate responses to infection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1462-5814
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
153-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11260138-Cell Line, pubmed-meshheading:11260138-Drosophila Proteins, pubmed-meshheading:11260138-Escherichia coli, pubmed-meshheading:11260138-Humans, pubmed-meshheading:11260138-Immunity, Innate, pubmed-meshheading:11260138-Interleukin-8, pubmed-meshheading:11260138-Kidney, pubmed-meshheading:11260138-Lipid A, pubmed-meshheading:11260138-Membrane Glycoproteins, pubmed-meshheading:11260138-Polymerase Chain Reaction, pubmed-meshheading:11260138-Receptors, Cell Surface, pubmed-meshheading:11260138-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11260138-Toll-Like Receptor 4, pubmed-meshheading:11260138-Toll-Like Receptors, pubmed-meshheading:11260138-Tumor Cells, Cultured, pubmed-meshheading:11260138-Urinary Bladder, pubmed-meshheading:11260138-Urothelium
pubmed:year
2001
pubmed:articleTitle
Induction of innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ- and cell-specific expression of Toll-like receptors within the human urinary tract.
pubmed:affiliation
Microbiology and Tumour Biology Center, Karolinska Institutet, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't