Summary 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.

Dendritic cells (DC) are essential to the initiation of an immune response due to their unique ability to take-up and process Ag, translocate to lymph nodes, and present processed Ag to naive T cells. Many chemokines, chemokine receptors and other G protein-coupled receptors (GPCRs) are implicated in these various aspects of DC biology. Through microarray analysis, we compared expression levels of chemokines, their cognate receptors, and selected GPCRs in human monocytes and in vitro monocyte-derived immature and mature DC. Hierarchical clustering of gene expression clearly distinguishes the three cell types, most notably highlighting exceptional levels of expression of the GPCR GPR105 within the immature monocyte-derived DC (MDDC) gene cluster. Little or no expression was observed within the monocyte and mature MDDC cluster. Putative functionality of the GPR105 receptor was demonstrated by an observed calcium flux in immature MDDC treated with the potent GPR105 agonist, uridine 5′-diphosphoglucose (UDP-glucose), while no response to the nucleotide sugar was seen in monocytes and mature MDDC. This UDP-glucose-induced calcium response was, at least in part, pertussis toxin-sensitive. Moreover, immature MDDC from some donors treated with UDP-glucose exhibit an increase in expression of the costimulatory molecule CD86, which correlates with the intensity of the UDP-glucose-induced calcium flux. Together, these data demonstrate differential expression of GPR105 on immature and mature MDDC and suggest a role for the receptor and its agonist ligand in DC activation.