Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn's disease

Abstract

Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by prominent cellular infiltrates in the bowel wall. Chemokines are chemotactic cytokines that are able to promote leukocyte migration to areas of inflammation and are also able to initiate cell activation events. They have recently been implicated in the pathophysiology of many disease states. The aim of this study was to detail the degree and distribution of specific chemokines, interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, -2, and -3, and macrophage inflammatory protein (MIP)-1alpha and -1beta, in IBD mucosa. Thirty-nine patients were included, ten controls, 20 ulcerative colitis (UC), and nine Crohn's disease (CD), with a range of disease activity. Colonic mucosal biopsies were collected from UC, CD, and control patients and embedded in glycol methacrylate. Two-micrometre-thick sections were cut and stained using immunohistochemistry for chemokine protein expression. Sections were analysed using a light microscope. Expression of all types of chemokine protein was detected in colonic mucosa from both control and IBD patients. Patterns of staining between IBD patients and controls differed significantly, but CD and UC patients demonstrated similar patterns of staining. Individual chemokine expression was found to be significantly up-regulated in IBD when patients were compared with the non-diseased group in all areas of the mucosal sections. Up-regulated chemokine expression correlated with increasing activity of the disease. It is concluded that human colonic chemokine expression is non-selectively up-regulated in IBD. The results supported the hypothesis that the degree of local inflammation and tissue damage in UC and CD is dependent on local expression of specific chemokines within IBD tissues.

Accumulation of CCR5+ T cells around RANTES+ granulomas in Crohn's disease: a pivotal site of Th1-shifted immune response?

“…13,14 We further obtained the same results concerning CCR5 in the present study. As a novelty, the present study has showed that noncaseating granulomas, specifically observed in Crohn's disease, express both protein and mRNA for RANTES, and that they are consistently surrounded by T cells expressing CCR5 and CXCR3.…”

“…[6][7][8] CCR5 is the shared receptor for macrophage inflammatory protein-1a (MIP-1a/CCL3), MIP-1b/CCL4, and regulated upon activation, normal T cell expressed and secreted (RANTES/CCL5), while CXCR3 is the shared receptor of interferon-inducible protein-10 (IP10/ CXCL10), monokine induced by IFN-g (Mig/CXCL9), and interferon-inducible T-cell alpha chemoattractant (I-TAC/CXCL11), which are all commonly inducible by IFN-g. 4,9 In IBD, upregulation of chemokines such as interleukin-8 (IL-8/CXCL8), 10,11 monocyte chemoattractant protein-1 (MCP-1/CCL2), and RANTES has been reported. 12 However, no significant differences were noted between ulcerative colitis and Crohn's disease in terms of expression of chemokines 13 or CXCR3 14 as long as the mucosal inflammation is concerned. The present study was set up to examine the involvement of chemokines and their receptors in IBD from the standpoint of Th1 and Th2-immune responses.…”

Anti-inflammatory activity of probiotic Bifidobacterium: Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells

“…In this study, the two heat-killed probiotic bacterial strains in BFM induced the secretion of IL-10 in PBMNC isolated from UC patients. It has been found that the degree of local inflammation and tissue damage in patients with IBD is dependent on the local expression of specific chemokines within affected tissues [16] . IL-8 protein [17] and mRNA [18] expression are associated with inflammation in UC.…”

“…A genetically engineered Lactococcus lactis thy12 producing IL-10 ameliorated colitis in two models of experimental colitis, providing proof of principal that topically delivers IL-10, can be therapeutically efficacious [14] and a recent proof-or-principle experiment using this transgenic bacterium expressing IL-10 in 10 patients with Crohn's disease showed efficacy [15] . In addition, there is an increasing amount of evidence to suggest that the potent neutrophil chemoattractant, IL-8, has an important role in the pathogenesis of inflammatory bowel disease (IBD) [16][17][18][19] . Recently, a higher concentration of IL-8 was found in more histologically inflamed tissue segments from pediatric IBD patients, suggesting that IL-8-specific therapies may universally modify the inflammatory activity in IBD patients [20] .…”

Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation

“…TLR5 engagement by bacterial flagellin activates mitogen-activated protein kinases and NF-B-related pathways, leading to macrophage inflammatory protein 3␣ (MIP3␣) and IL-8 production (12). Because colonic inflammation in IBD patients is characterized by increased MIP3␣ and IL-8 production (13,14), we hypothesized that TLR5-mediated responses are involved in colonic inflammation. Indeed, bacterial flagellin recently was described as a dominant antigen in IBD patients, and flagellin-specific CD4 ϩ T cells were able to induce colonic inflammation in an adoptive CD4 ϩ T cell transfer model of colitis (15).…”