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Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa.

Samuelsson, Patrik LU ; Hang, Long; Wullt, Björn LU ; Irjala, Heikki LU and Svanborg, Catharina LU (2004) In Infection and Immunity 72(6). p.3179-3186
Abstract
Mucosal pathogens trigger a local innate host response by activating epithelial cells. Bacterial adherence and Toll-like receptor 4 (TLR4) signaling have been implicated as key events in this process. This study addressed the molecular basis of the epithelial response to gram-negative infection in the human urinary tract. Mucosal biopsies were obtained from kidneys, ureters, and bladders of patients undergoing urinary tract surgery, and epithelial TLR4 and CD14 expression was examined by immunohistochemistry. TLR4 was detected in epithelial cells lining the entire urinary tract and in the renal tubular epithelium. CD14, in contrast, was completely absent from the epithelial tissue. The response of the epithelial cells to infection was... (More)
Mucosal pathogens trigger a local innate host response by activating epithelial cells. Bacterial adherence and Toll-like receptor 4 (TLR4) signaling have been implicated as key events in this process. This study addressed the molecular basis of the epithelial response to gram-negative infection in the human urinary tract. Mucosal biopsies were obtained from kidneys, ureters, and bladders of patients undergoing urinary tract surgery, and epithelial TLR4 and CD14 expression was examined by immunohistochemistry. TLR4 was detected in epithelial cells lining the entire urinary tract and in the renal tubular epithelium. CD14, in contrast, was completely absent from the epithelial tissue. The response of the epithelial cells to infection was studied by in vitro challenge of the biopsies with uropathogenic Escherichia coli bacteria. A rapid cytokine response was observed, with production of interleukin-1ß (IL-1ß), IL-6, and IL-8 but not of IL-4 or gamma interferon. Adhering, P- or type 1-fimbriated E. coli activated IL-6 and IL-8 production more efficiently than the nonfimbriated control, as shown by cellular staining and analysis of secreted cytokines. The results demonstrate that human uroepithelial cells possess the molecular machinery needed to respond to uropathogenic E. coli. This includes recognition receptors for fimbriae and TLR4 for transmembrane signaling. We speculate that the lack of membrane-bound CD14 allows the epithelium to regulate its sensitivity to lipopolysaccharide and to discriminate between more-virulent and less-virulent strains. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
72
issue
6
pages
3179 - 3186
publisher
American Society for Microbiology
external identifiers
  • wos:000221662400011
  • pmid:15155619
  • scopus:2542530840
ISSN
1098-5522
DOI
10.1128/IAI.72.6.3179-3186.2004
language
English
LU publication?
yes
id
1df5d2d0-7054-482c-bb26-95e86660fe1f (old id 123322)
date added to LUP
2007-07-04 10:57:04
date last changed
2017-10-29 03:24:04
@article{1df5d2d0-7054-482c-bb26-95e86660fe1f,
  abstract     = {Mucosal pathogens trigger a local innate host response by activating epithelial cells. Bacterial adherence and Toll-like receptor 4 (TLR4) signaling have been implicated as key events in this process. This study addressed the molecular basis of the epithelial response to gram-negative infection in the human urinary tract. Mucosal biopsies were obtained from kidneys, ureters, and bladders of patients undergoing urinary tract surgery, and epithelial TLR4 and CD14 expression was examined by immunohistochemistry. TLR4 was detected in epithelial cells lining the entire urinary tract and in the renal tubular epithelium. CD14, in contrast, was completely absent from the epithelial tissue. The response of the epithelial cells to infection was studied by in vitro challenge of the biopsies with uropathogenic Escherichia coli bacteria. A rapid cytokine response was observed, with production of interleukin-1ß (IL-1ß), IL-6, and IL-8 but not of IL-4 or gamma interferon. Adhering, P- or type 1-fimbriated E. coli activated IL-6 and IL-8 production more efficiently than the nonfimbriated control, as shown by cellular staining and analysis of secreted cytokines. The results demonstrate that human uroepithelial cells possess the molecular machinery needed to respond to uropathogenic E. coli. This includes recognition receptors for fimbriae and TLR4 for transmembrane signaling. We speculate that the lack of membrane-bound CD14 allows the epithelium to regulate its sensitivity to lipopolysaccharide and to discriminate between more-virulent and less-virulent strains.},
  author       = {Samuelsson, Patrik and Hang, Long and Wullt, Björn and Irjala, Heikki and Svanborg, Catharina},
  issn         = {1098-5522},
  language     = {eng},
  number       = {6},
  pages        = {3179--3186},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa.},
  url          = {http://dx.doi.org/10.1128/IAI.72.6.3179-3186.2004},
  volume       = {72},
  year         = {2004},
}