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

Abstract

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.

A Novel Peroxisome Proliferator-activated Receptor (PPAR)γ Agonist 2-Hydroxyethyl 5-chloro-4,5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis

“…Dysregulated cytokine production has been implicated in the pathogenesis of IBD (42), and chemokines such as CXCL1, CXCL2, CXCL3, and CCL20 are expressed specifically in inflamed areas of IBD colon (22). NF-B is also activated in macrophages and epithelial cells of inflamed intestinal mucosa and its activation induces transcription of pro-inflammatory cytokines and chemokines, suggesting a crucial role in inflammatory diseases (16,18).…”

“…Decreased Inflammatory Chemokine Expression by J11-ClPrevious studies revealed that several chemokines, such as CXCL1, CXCL2, CXCL3, and CCL20 are up-regulated specifically in the inflamed colon of IBD patients (22). In NCM460 cells, TNF-␣-mediated increase of the inflammatory chemokines CCL20, CXCL2, CXCL3, and CX3CL1 was significantly reduced by pretreatment with J11-Cl (Fig.…”

The polymorphism and gene expression of chemokine receptor 6 is associated with digestive disorders in rabbits

“…Similar results in human were also obtained. Puleston et al (2005) indicated that CCR6 gene expression was increased in colonic of IBD patients. As for the mechanism, it can be attributed to the chemokines' function that recruit inflammation leukocyte to against inflammation intensifies.…”

CCR6-CCL20 Axis in IBD: What have we learnt in the past 20 years?

“…An examination of Caco-2 and HT-29 cell lines had shown a similar expression of these chemokines when stimulated by IL-1β. Caco-2 cells were unresponsive to TNF-α although both IL-1 β and TNF-α synergistically activated HT-29 and primary keratinocytes indicating that these two cytokines prominently influence the epithelial chemokine expression in inflamed tissue of IBD patients [42].…”