Inflammatory bowel disease (IBD) is characterised by intense mucosal recruitment of activated leukocytes.
Chemokines determine inflammatory leukocyte recruitment and retention.
Dr Platt and colleagues from England undertook a study in order to compare the expression of the entire chemokine family within colonic mucosa from IBD patients and uninflamed controls.
The investigators hybridized a microarray of cDNAs, representing every member of this superfamily and their cognate receptors, with probes derived from colonoscopic biopsies.
The researchers found that a distinct subset of chemokines, consisting of CXCLs 13 and 8 and CCL20, was upregulated in active colonic IBD, compared with uninflamed areas or tissue from controls.
| Researchers found a chemokine response in Caco-2 cells by stimulation with interleukin (IL)-1, but not tumour necrosis factor-alpha (TNF-)|
|Alimentary Pharmacology and Therapeutics|
In addition, the research team confirmed increased expression of their cognate receptors, CXCR1, CXCR2 and CCR6, by quantitative PCR and immunohistochemistry.
The researchers were able to induce an identical chemokine response in Caco-2 cells by stimulation with interleukin (IL)-1, but not tumour necrosis factor-alpha (TNF-).
By contrast, IL-1 and TNF- were synergistic in an HT29 cell line and primary keratinocytes.
Dr Platt concluded, "IL-1 and TNF- appear to be the pivotal mediators of a previously unidentified coordinated epithelial chemokine response that dominates the mucosal chemokine environment in inflamed IBD tissue."