Immunolocalization and expression of kinin B₁R and B₂R receptors in human inflammatory bowel disease

Abstract

Bradykinin is a mediator of inflammation, responsible for pain, vasodilation, and capillary permeability. Bradykinin receptor 1 (B1R) and bradykinin receptor 2 (B2R) are G protein-coupled receptors that mediate kinin effects. The latter is constitutive and rapidly desensitized; the former is induced by inflammatory cytokines and resistant to densensitization. The distribution of bradykinin receptors in human intestinal tissue was studied in patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD). Both B2R and B1R proteins are expressed in the epithelial cells of normal and IBD intestines. B1R protein is visualized in macrophages at the center of granulomas in CD. B2R protein is normally present in the apexes of enterocytes in the basal area and intracellularly in inflammatory tissue. In contrast, B1R protein is found in the basal area of enterocytes in normal intestine but in the apical portion of enterocytes in inflamed tissue. B1R protein is significantly increased in both active UC and CD intestines compared with controls. In patients with active UC, B1R mRNA is significantly higher than B2R mRNA. However, in inactive UC patients, the B1R and B2R mRNA did not differ significantly. Thus bradykinin receptors in IBD may reflect intestinal inflammation. Increased B1R gene and protein expression in active IBD provides a structural basis of the important role of bradykinin in chronic inflammation.

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

“…BK-receptor expression in inflammatory bowel disease, namely, ulcerative colitis and Crohn's disease, may be altered in intestinal inflammation. Increased B1R gene and protein expression in active inflammatory bowel disease provides a structural basis for the important role of kinins in chronic inflammation (303).…”

The role of the complement and contact systems in the dextran sulfate sodium-induced colitis model: the effect of C1 inhibitor in inflammatory bowel disease

“…The kallikrein-kinin system consists of circulating kininogens, the proteolytic enzymes factor XII and prekallikrein, kinins, and two G protein-coupled receptors termed kinin B 1 and bradykinin B 2 receptors, which mediate the biological effects of kinins (1,24). Both B 1 and B 2 receptors have been immunolocalized in the epithelial cells of affected human intestinal tissue (38). A kinin B 1 antagonist attenuates the inflammatory changes in the experimental colitis model (17).…”

Kallikrein – Kinin System and Coagulation System in Inflammatory Bowel Diseases

“…In dextran sulfate (DDS) -induced colitis model in mice a selective B2R antagonist suppressed shortening of the large intestine (Arai et al, 1999), which was in agreement with future results indicated that intestinal contraction was regulated by B2R (Hara et al, 2007), however demonstrated only limited effect in intestinal inflammatory lesions. Later in human studies we demonstrated the increase in the ratio of B1R to B2R gene expression in relation to the degree of intestinal inflammation, and visualized both B1R and B2R in normal as well as inflammatory human colon and ileum (Stadnicki et al, 2005). B2R protein was normally present in the apices of enterocytes in the basal area and intracellularly in inflammatory tissue.…”