Vitamin D regulates the tight-junction protein expression in active ulcerative colitis

ABSTRACT Objective: Epithelial barrier function is primarily regulated by the tight-junction proteins. Ulcerative colitis (UC) is characterized by Th2 immune response with inflammation and epithelial barrier dysfunction, including an elevation of claudin-2 protein function. Recent studies support an important role of vitamin D in the pathogenesis as well as potential therapy of IBD. Vitamin D deficiency is in fact common in patients with IBD. The aim of the study was to determine whether vitamin D could affect IL-13 and IL-6 levels, and regulate the activity of tight-junction proteins. Claudin-1, -2, -4, and -7 in the inflamed and non-inflamed colonic mucosa of UC patients. Material and methods: Biopsies from inflamed and non-inflamed tract of colon and rectum from the same active UC patients were cultured with1,25(OH)2D3. IL-13, IL-6 and the tight-junction proteins level were determined. Results: Claudin-1 and claudin-2 proteins were up-regulated in active UC. The treatment with 1,25(OH)2D3 decreases the claudin-1 and claudin-2 protein levels in both inflamed and non-inflamed tract. Claudin-4 and claudin-7 proteins were down-regulated and their levels increase after incubation with the 1,25(OH)2D3. When the biopsies were incubated with 1,25(OH)2D3, a decrease in IL-13 and IL-6 levels was registered. Conclusions: Our results, indicating the inhibition of cytokine levels and the regulation of claudin-2, claudin-4, and claudin-7 by 1,25(OH)2D3, suggest that vitamin D may represent a potential therapeutic agent for the treatment of active UC.