title: A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) is characterised by intense mucosal recruitment of activated leukocytes. Chemokines determine inflammatory leukocyte recruitment and retention.
  
  
  OBJECTIVE
  To compare expression of the entire chemokine family within colonic mucosa from IBD patients and uninflamed controls.
  
  
  METHODS
  A microarray of cDNAs, representing every member of this superfamily and their cognate receptors, was hybridised with probes derived from colonoscopic biopsies.
  
  
  RESULTS
  A distinct subset of chemokines, consisting of CXCLs 1-3 and 8 and CCL20, was upregulated in active colonic IBD, compared with uninflamed areas or tissue from controls. Increased expression of their cognate receptors, CXCR1, CXCR2 and CCR6, was confirmed by quantitative PCR and immunohistochemistry. An identical chemokine response was induced in Caco-2 cells by stimulation with interleukin (IL)-1beta, but not tumour necrosis factor-alpha (TNF-alpha). By contrast, IL-1beta and TNF-alpha were synergistic in an HT29 cell line and primary keratinocytes.
  
  
  CONCLUSIONS
  IL-1beta and TNF-alpha appear to be the pivotal mediators of a previously unidentified coordinated epithelial chemokine response that dominates the mucosal chemokine environment in inflamed IBD tissue.
authors.affiliation: Centre for Gastroenterology, Royal Free Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Puleston
authors.forename: M
authors.initials: M
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: Murch
authors.forename: K
authors.initials: K
authors.lastname: Bid
authors.forename: S
authors.initials: S
authors.lastname: Makh
authors.forename: P
authors.initials: P
authors.lastname: Ashwood
authors.forename: A H
authors.initials: AH
authors.lastname: Bingham
authors.forename: H
authors.initials: H
authors.lastname: Green
authors.forename: P
authors.initials: P
authors.lastname: Moss
authors.forename: A
authors.initials: A
authors.lastname: Dhillon
authors.forename: R
authors.initials: R
authors.lastname: Morris
authors.forename: S
authors.initials: S
authors.lastname: Strobel
authors.forename: R
authors.initials: R
authors.lastname: Gelinas
authors.forename: R E
authors.initials: RE
authors.lastname: Pounder
authors.forename: A
authors.initials: A
authors.lastname: Platt
mesh_terms: D018938:Caco-2 Cells; D018925:Chemokines / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha