TITLE

A DISTINCT SUBSET OF CHEMOKINES, INDUCED IN COLONIC EPITHELIUM BY IL-1β, DOMINATES THE MUCOSAL CHEMOKINE RESPONSE IN ULCERATIVE COLITIS

AUTHOR(S)
Puleston, J.; Cooper, M.; Murch, S.; Makh, S.; Ashwood, P.; Torrente, F.; Bingham, A.; Green, H.; Moss, P.; Dhillon, A.; Gelinas, R.; Pounder, R.; Platt, A.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA59
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Purpose: Inflammatory bowel disease (IBD) is characterised by intense mucosal recruitment of activated leukocytes. As chemokines determine inflammatory leukocyte recruitment and retention, we compared expression of the entire chemokine family within colonic mucosa from IBD patients and uninflamed controls. Methods: A microarray, representing every member of this superfamily and their cognate receptors, was hybridised with probes derived from colonoscopic biopsies. The array levels were correlated with histopathological inflammatory scores and expression of their cognate receptors by quantitative PCR and immunohistochemistry. Flow cytometry was performed on mucosally-derived colonic cells. Caco-2 and keratinocyte cell lines were stimulated with IL-1β and TNF-α, and analysed using the same microarray. Results: A distinct subset of chemokines, consisting of CXCLs 1-3 and 8 and CCL20, was upregulated in active colonic IBD, compared to uninflamed areas or tissue from controls. This corresponded to histopathological scores. Increased expression of their cognate receptors, CXCR1, CXCR2, and CCR6, was confirmed by quantitative PCR and immunohistochemistry Flow cytometric revealed an increase of CCL20 expression on epithelial cells in IBD specimens, particularly in severe disease. An identical chemokine response was induced in Caco-2 cells by stimulation with lL-1β, but not TNF-α. By contrast, IL-1β and TNF-α were synergistic in keratinocytes. Conclusion: lL-1β appears to be the pivotal mediator of an epithelial response that dominates the mucosal chemokine environment in ulcerative colitis. These data suggest several new therapeutic targets for IBD, as well as identifying a previously unrecognised co-ordinated epithelial chemokine response.
ACCESSION #
9747683

 

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