腺苷A3受体在溃疡性结肠炎患者结肠黏膜中的异常表达和作用

Abstract

Objective: An attempt was made in this paper to study the role of adenosine A3 receptor/NF-κB signaling pathway in pathogenesis of ulcerative colitis.Methods: The colonic mucosa tissues of patients with ulcerative colitis were obtained by colonoscopy.The distribution and expression of adenosine A3 receptor were detected by immunofluorescence and western blotting while the colocalization of adenosine A3 receptor and NF-κB p65 in colonic mucosal epithelial cells were detected by immunofluorescence assay.Besides,the effects of adenosine A3 receptor agonist 2-Cl-IB-MECA on NF-κB signaling pathway and expression level of the downstream inflammatory cytokines IL-8 and IL-1βof human colonic epithelial cell line HT-29 were detected.Results: In the colon mucosa epithelium from patients with ulcerative colitis,the expression of adenosine A3 receptor was significantly decreased compared with that in the normal controls(P<0.01).The adenosine A3 receptor and NF-κB p65 were co-localized in colonic mucosa epithelial cells,and NF-κB p65 translocated from cytoplasm to nucleus.Compared with the controls,2-Cl-IB-MECA significantly reduced the nuclear translocation of NF-κB p65 and its expression level in the nucleus of human colonic epithelial cells,and reduced the protein secretion of IL-8 and IL-1βinduced by TNF-α(P<0.05).Conclusions: Adenosine A3 receptor downregulation together with nuclear translocation of NF-κB occur in colonic mucosa epithelial cells of patients with ulcerative colitis.The activation of adenosine A3 receptor can play an anti-inflammatory role through inhibiting NF-κB signaling pathway and the expression of downstream inflammatory cytokines in human colon epithelial cells.Adenosine A3 receptor may be a therapeutic target in patients with ulcerative colitis.