Distribution of the interleukin-8 receptors, CXCR1 and CXCR2, in inflamed gut tissue

Abstract

There is increasing evidence to suggest that the potent neutrophil chemoattractant interleukin-8 (IL-8) has an important role in the pathogenesis of inflammatory bowel disease. IL-8 mediates its actions via two cell surface receptors, CXCR1 and CXCR2. This paper describes the distribution of these IL-8 receptors in the normal gastrointestinal tract and how this is modified in ulcerative colitis (UC). Paraffin-embedded colonic resection specimens were stained with monoclonal antibodies directed against CXCR1 and CXCR2 in ten cases of total UC, 16 cases of appendicitis, and 11 histologically normal sections. A semiquantitative scale of 0-4 was used to assess the proportion and intensity of positively stained cells within certain defined areas of tissue. A comparative assessment was made of the distribution of various cell populations. Dual immunostaining was used to confirm the phenotype of positively staining cells. In the histologically normal colon, the antibody against CXCR1 stained a subpopulation of macrophages deep to the epithelium and germinal centre lymphocytes. A similar pattern of staining was seen in acute appendicitis, with in addition some positively stained neutrophil polymorphs. In UC, there was up-regulation of CXCR1, with a striking increase in positively stained macrophages throughout the mucosa and of B and T lymphocytes outside the germinal centre areas. There was also intense up-regulation of CXCR1 expression by the luminal epithelium, reflected in the epithelial staining score (mean+/-SE=1.8+/-0.44 for UC cases, vs. 0.23+/-0.16 for controls and 0.25+/-0.14 for acute appendicitis). CXCR2 was only expressed on a small population of lamina propria mononuclear cells and crypt epithelial cells, with no significant differences observed between the groups. These results suggest that IL-8 may, through CXCR1, have a role beyond neutrophil recruitment in mediating the immune response in UC and that this is not merely a consequence of the acute inflammation seen in UC.

Clotrimazole Ameliorates Intestinal Inflammation and Abnormal Angiogenesis by Inhibiting Interleukin-8 Expression through a Nuclear Factor-κB-Dependent Manner

“…In fact, IL-8 increase has been observed in inflamed intestinal mucosa of patients with chronic IBD, implying an important role in the pathogenesis of IBD (Daig et al, 1996;Williams et al, 2000). In agreement with previous reports for IL-8 induction (Murayama et al, 1997;Brasier et al, 1998), our result also demonstrated that IL-8 expression was barely detectable in vehicle-treated HT29 cells or rat colon tissue, and TNBS (Fig.…”

Constitutive expression of MMP9 in intestinal epithelium worsens murine acute colitis and is associated with increased levels of proinflammatory cytokine Kc

“…Williams et al (53) have reported the presence of these two receptors in normal GI tract and also about their modification in inflamed gut tissue. They observed that CXCR1 are strongly upregulated in the mucosal epithelium, specifically and commonly on morphologically damaged surface epithelium (53), whereas the role and distribution of CXCR2 in GI tract has not been well explored.…”

“…It has been well documented in literature that cytokines are involved in the dysregulated inflammatory response in IBD, although the exact mechanism is still unknown. Different studies have reported that IL-8 (mouse homologue is Kc), which is a potent cytokine for recruitment and activation of neutrophils and plays an active role in the induction and promotion of IBD (16,32,34,49,52,53), although none of these studies could delineate the exact mechanism by which IL-8 mediates or propagates inflammation in IBD. Furthermore, Singer and Sansonetti (46) demonstrated that intraluminal addition of recombinant IL-8 was directly associated with the development of acute invasive Shigella-induced colitis.…”

“…They observed that CXCR1 are strongly upregulated in the mucosal epithelium, specifically and commonly on morphologically damaged surface epithelium (53), whereas the role and distribution of CXCR2 in GI tract has not been well explored. Recently, Shea-Donohue et al (44) have shown the protective role of the CXCR2 ligand CXCL1 in DSS-induced colitis in murine model, which, however, contradicts the findings reported by Buanne et al (11).…”

Lactobacillus plantarum CQPC06 Activity Prevents Dextran Sulfate Sodium‐Induced Colitis by Regulating the IL‐8 Pathway

“…When IL‐8 combines with CXCR1/2, CXCR1/2 transduces signals via G‐protein coupled receptors (Han, Feng, Chen, Gerard, & Boisvert, ). CXCR1 and CXCR2 are primarily expressed on the surfaces of T cells, monocytes, monocytoid B cells, melanoma cells, synovial fibroblasts, neutrophils, and myeloid progenitor cells (Williams et al., ). During acute inflammation, chemokines interact with the glycosaminoglycans on the surfaces of endothelial cells.…”