Chemokines in Inflammatory Bowel Diseases

Abstract

Uncontrolled activation of mucosal effector cells has been identified as the main pathogenic mechanism involved in the initiation and perpetuation of mucosal inflammation in inflammatory bowel diseases (IBD). The sustained activation of these cells leads to the aberrant production of various pro-inflammatory mediators, which co-ordinated action amplifies the inflammatory process. In this setting a network of tissue-specific chemoattractant cytokines (chemokines) and their corresponding receptors have been implicated as main contributors in the initiation and perpetuation of the inflammatory reaction in IBD. They are produced by a variety of inflammatory cells present in IBD lesions, as well as endothelial and epithelial cells. Chemokines not only control the multistep process of leukocyte adhesion to and migration across the endothelium, but also the release of lipid mediators and oxygen radicals from leukocytes, the modulation of tumorigenesis, release of matrix metalloproteinases and tissue fibrosis. Numerous data indicate that that intestinal chemokine expression is non-selectively up-regulated in IBD and correlates with disease activity. The development of selective inhibitors for chemokines or chemokine receptors, based on a more complete understanding of the immunopathogenic role of chemokines in intestinal inflammation, will be of great interest as potential novel therapeutic strategies in IBD.

Interleukin-8, CXCL1, and MicroRNA miR-146a Responses to Probiotic Escherichia coli Nissle 1917 and Enteropathogenic E. coli in Human Intestinal Epithelial T84 and Monocytic THP-1 Cells after Apical or Basolateral Infection

“…In the context of inflammatory bowel diseases (IBD), such as ulcerative colitis or Crohn's disease, the complexity of the signaling interplay increases even further as inflammatory immune reactions are triggered and perpetuated, involving, e.g., a network of chemoattractant cytokines (chemokines) (11)(12)(13) and miRNA signatures (14)(15)(16).…”

L13a-dependent translational control in macrophages limits the pathogenesis of colitis

“…(c) The plasma samples from control and KO mice were subjected to endotoxin assay using Pierce LAL chromogenic endotoxin quantitation kit. n 5 4 per group for regular drinking water-fed mice and n 5 10 per group for DSS-containing water-fed mice.L13a deficiency promotes colitis D Poddar et al role of inflammatory cytokines 6 and chemokines30,31 in the pathogenesis of UC has recently been well appreciated. The chemokine-mediated aberrant chemoattraction of leukocytes in the inflamed intestinal epithelium promotes the destruction of epithelial crypts.…”

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

“…These effector cell over activation is said to initiate and sustain inflammation in the gut mucosa and are amply aided by chemokines which help leukocyte adhesion and migration to sites of injury. Among the numerous functions of chemokines, they had listed out the secretion of lipid mediators and reactive oxygen species from leukocytes, matrix release of metalloproteinase, stimulation of tissue fibrosis and tumorigenesis [19].…”