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A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease

  • J Puleston
  • , M Cooper
  • , S Murch
  • , K Bid
  • , S Makh
  • , P Ashwood
  • , A H Bingham
  • , H Green
  • , P Moss
  • , A Dhillon
  • , R Morris
  • , S Strobel
  • , R Gelinas
  • , R E Pounder
  • , A Platt

Research output: Contribution to journal › Article (Academic Journal) › peer-review

110 Citations (Scopus)

Abstract

BACKGROUND: Inflammatory bowel disease (IBD) is characterised by intense mucosal recruitment of activated leukocytes. Chemokines determine inflammatory leukocyte recruitment and retention.

AIM: 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.

Original languageEnglish
Pages (from-to)109-20
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume21
Issue number2
DOIs
Publication statusPublished - 15 Jan 2005

Keywords

  • Caco-2 Cells
  • Chemokines
  • Flow Cytometry
  • Humans
  • Inflammatory Bowel Diseases
  • Interleukin-1
  • Intestinal Mucosa
  • Tumor Necrosis Factor-alpha
  • Up-Regulation

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