OBJECTIVES AND BACKGROUND: Recently, a possible role of circadian system in the pathogenesis of various gastrointestinal disorders gained an attention. The association of circadian system with immune system activity and reciprocal connection with intestinal microbiota indicate possible links with inflammatory bowel diseases (IBD).
METHODS: The retrospective study provided a semiquantitative immunohistochemical analysis of the expression of 8 core circadian proteins (BMAL1, BMAL2, PER1, PER2, PER3, CLOCK, NPAS2 and TIMELESS) in the epithelial cells of intestinal mucosa in 24 patients with Crohn's disease (CD) and 26 patients with ulcerative colitis (UC). Samples from patients without history of IBD served as the control. The BMAL1 protein expression in intramucosal inflammatory cells was explored as well.
RESULTS: The expression of 5 core circadian proteins (BMAL1, PER1, PER3, TIMELESS and NAPS2) was decreased in mucosal epithelium of patients with IBD in comparison with the control samples, whereas the expression of BMAL1 and PER1 was more noticeably decreased in UC patients and PER3, TIMELESS and NPAS2 in CD patients. There was a decreased BMAL1 expression in intramucosal inflammatory cells of IBD patients.
CONCLUSION: Decreased core circadian proteins expression in colonic mucosa and in intramucosal inflammatory cells of IBD patients indicated a circadian rhythm deregulation as contributing factor in the development of IBD. To our knowledge, this is so far the most extensive immunohistochemical analysis performed on the samples of IBD patients evaluating the changes in circadian protein expression in the intestinal mucosa (Tab. 1, Fig. 2, Ref. 31).
