title: Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1.
abstract: BACKGROUND
  In the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.
  
  
  RESULTS
  In the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.
  
  
  CONCLUSIONS
  These results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen.
authors.forename: Oriana
authors.initials: O
authors.lastname: Rossi
authors.forename: Jurgen
authors.initials: J
authors.lastname: Karczewski
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Stolte
authors.forename: Robert J M
authors.initials: RJ
authors.lastname: Brummer
authors.forename: Michiel A
authors.initials: MA
authors.lastname: van Nieuwenhoven
authors.forename: Marjolein
authors.initials: M
authors.lastname: Meijerink
authors.forename: Joost R J
authors.initials: JR
authors.lastname: van Neerven
authors.forename: Sven C D
authors.initials: SC
authors.lastname: van Ijzendoorn
authors.forename: Peter
authors.initials: P
authors.lastname: van Baarlen
authors.affiliation: Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands. jerry.wells@wur.nl.
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Wells
mesh_terms: D019898:Autocrine Communication / Q000235:genetics*; D018938:Caco-2 Cells; D016764:Cell Polarity; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055666:Lipopeptides / Q000494:pharmacology; D025941:Protein Interaction Mapping; D023062:Receptors, Interleukin-8A / Q000235:genetics* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; C560312:Pam2CSK4 lipopeptide; D023062:Receptors, Interleukin-8A; C495342:TLR2 protein, human; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051198:Toll-Like Receptor 5