Comparative Expression of Vitamin D Receptor and Cathelicidin in Human Intestinal Mucosa in Persons With and Without Inflammatory Bowel Disease

Abstract

Background: Vitamin D receptor (VDR) expression has been demonstrated to be lower in explanted colons of patients with Ulcerative Colitis (UC) compared to patients without Inflammatory Bowel Disease (IBD). Similar studies are not available with Crohn's disease (CD). VitaminD has been shown to induce expression of the antimicrobial protein cathelicidin in multiple cell lines, whereas expression of cathelicidin has been shown to be blunted in patients with CD. Objectives: To quantify the expression of the VDR, CYP24A and CYP27B, and cathelicidin in colonic and ileal mucosa of patients with IBD when compared to healthy controls, and to correlate this expression with endoscopically visualized mucosal inflammation in patients with IBD. Methods: Patient undergoing colonoscopy for colorectal cancer screening were invited to participate in this study, as were patients undergoing colonoscopy for either diagnosis or follow-up of IBD. Endoscopic findings were noted. Biopsies were obtained from the rectum and terminal ileum in all patients. Biopsies were obtained from areas of active inflammation in patients with IBD. Pathology reports were reviewed when biopsies were obtained for diagnostic or surveillance purposes. Real Time PCR was performed on samples for VDR, CYP24A, CYP27B and cathelicidin. Immunofluorescent staining was also performed for VDR expression. Results: Forty-two patients were recruited: 27 without IBD, 10 with UC, and 5 with CD. Five patients had endoscopic evidence of active disease with erythema, nodularity, or ulceration. PCR revealed measurable expression of VDR, CYP24A, and cathelicidin in controls and subjects. Minimal expression of CYP27B was present in either controls or subjects. Intestinal mucosa from patients with IBD had decreased mRNA transcripts of VDR compared to those without IBD (p <0.05). There was a trend of increased mRNA transcripts of cathelicidin in the intestinal mucosa from subjects with IBD compared to controls. Results were not statistically significant. Immunostaining revealed prominent VDR expression in normal intestinal epithelium. Intestinal epithelial VDR expression by immunostaining is decreased in endoscopically apparent areas of active IBD when compared with controls. Epithelial VDR expression by immunostaining in IBD samples without active disease was similar to controls. Conclusions: VDR is expressed in healthy intestinal epithelial cells. Intestinal epithelial VDR expression is decreased in patients with active UC and CD when compared to healthy controls, and when compared to IBD patients with inactive disease. Since vitamin D administration enhances VDR expression, a clinical study with vitamin D administration in patients with UC and CD is warranted to confirm the role of VDR in the pathophysiology of IBD.