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.

Keywords:

• Tight-junctions proteins
• ulcerative colitis
• vitamin D

Acknowledgements

We are grateful to the collaboration of Dr Monica Milla, the director of ‘Centro di Riferimento per le Malattie Croniche Intestinali’ of Florence (Italy).

Disclosure statement

The authors declare that they have no conflicts of interest.

Funding information

This study was supported by grants from MIUR.