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

J. Puleston, M. Cooper, S. Murch, K. Bid, S. Makh, Paul 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 journalArticle

81 Scopus citations

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)-1β, but not tumour necrosis factor-alpha (TNF-α). By contrast, IL-1β and TNF-α were synergistic in an HT29 cell line and primary keratinocytes. Conclusions: IL-1β and TNF-α 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 (US)
Pages (from-to)109-120
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume21
Issue number2
DOIs
StatePublished - Jan 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Puleston, J., Cooper, M., Murch, S., Bid, K., Makh, S., Ashwood, P., Bingham, A. H., Green, H., Moss, P., Dhillon, A., Morris, R., Strobel, S., Gelinas, R., Pounder, R. E., & Platt, A. (2005). A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease. Alimentary Pharmacology and Therapeutics, 21(2), 109-120. https://doi.org/10.1111/j.1365-2036.2004.02262.x