Yukawa Tomomi, Oshitani Nobuhide, Yamagami Hirokazu, Watanabe Kenji, Higuchi Kazuhide, Arakawa Tetsuo
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Int J Mol Med. 2007 Aug;20(2):161-7.
There is conflicting evidence regarding the significance of vasoactive intestinal peptide (VIP) in inflammatory bowel disease (IBD). Involvement of the VIP receptor in IBD has not been reported. We examined the expression and localization of the VIP receptor in IBD. We determined the location of VIP receptor 1 (VIPR1) immunohistologically in surgically resected intestinal samples from 10 controls, 15 patients with ulcerative colitis, and 10 patients with Crohn's disease. A fluorescein-linked immunohistological study was performed using anti-VIPR1 antibody, with double-staining with antibodies to CD3, CD19, and CD68. Correlations with interleukin (IL)-4 and TNF-alpha expression were also investigated. Results showed that the number of VIPR1-positive cells was significantly increased in the inflammatory mucosa. VIPR1 was expressed in CD3-, CD19-, and CD68-positive cells. The proportion of VIPR1-positive cells among CD3-positive cells was significantly higher in the lamina propria of patients with ulcerative colitis than in those with Crohn's disease and the controls. The proportion of VIPR1-positive cells among CD68-positive cells was significantly higher in patients with ulcerative colitis and Crohn's disease than in the controls. A correlation between the numbers of VIPR1- and IL-4-positive cells was found in patients with ulcerative colitis, and between the numbers of VIPR1- and TNF-alpha-positive cells in patients with Crohn's disease. In conclusion, VIPR1 was widely expressed in infiltrating inflammatory cells, especially CD3- and CD68-positive cells in ulcerative colitis mucosa and CD68-positive cells in Crohn's disease mucosa. The differential expression of VIPR1 in ulcerative colitis and Crohn's disease mucosa suggests that the VIP system plays different roles in the pathogenesis of IBD.
关于血管活性肠肽(VIP)在炎症性肠病(IBD)中的意义,存在相互矛盾的证据。尚未有关于VIP受体参与IBD的报道。我们研究了IBD中VIP受体的表达和定位。我们通过免疫组织化学方法确定了10名对照者、15名溃疡性结肠炎患者和10名克罗恩病患者手术切除的肠道样本中VIP受体1(VIPR1)的位置。使用抗VIPR1抗体进行荧光素标记的免疫组织学研究,并与抗CD3、CD19和CD68抗体进行双重染色。还研究了与白细胞介素(IL)-4和肿瘤坏死因子-α(TNF-α)表达的相关性。结果显示,炎症黏膜中VIPR1阳性细胞数量显著增加。VIPR1在CD3、CD19和CD68阳性细胞中表达。溃疡性结肠炎患者固有层中CD3阳性细胞中VIPR1阳性细胞的比例显著高于克罗恩病患者和对照者。溃疡性结肠炎和克罗恩病患者中CD68阳性细胞中VIPR1阳性细胞的比例显著高于对照者。在溃疡性结肠炎患者中发现VIPR1和IL-4阳性细胞数量之间存在相关性,在克罗恩病患者中发现VIPR1和TNF-α阳性细胞数量之间存在相关性。总之,VIPR1在浸润性炎症细胞中广泛表达,尤其是溃疡性结肠炎黏膜中的CD3和CD68阳性细胞以及克罗恩病黏膜中的CD68阳性细胞。VIPR1在溃疡性结肠炎和克罗恩病黏膜中的差异表达表明VIP系统在IBD发病机制中发挥不同作用。