Research article

Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury

Monica Froicu¹ and Margherita T Cantorna²

¹  Department of Veterinary and Biomedical Sciences, Pathobiology Graduate Program, The Pennsylvania State University, University Park, PA 16802, USA

²  Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Diseases, The Pennsylvania State University, University Park, PA 16802, USA

author email corresponding author email

BMC Immunology 2007, 8:5doi:10.1186/1471-2172-8-5

Published:	30 March 2007

Abstract

Background

The active form of vitamin D (1,25(OH)₂D₃) has been shown to inhibit development of inflammatory bowel disease (IBD) in IL-10 KO mice. Here, the role of the vitamin D receptor (VDR) and 1,25(OH)₂D₃ in acute experimental IBD was probed.

Results

VDR KO mice were extremely sensitive to dextran sodium sulfate (DSS) and there was increased mortality of the VDR KO mice at doses of DSS that only caused a mild form of colitis in wildtype (WT) mice. DSS colitis in the VDR KO mice was accompanied by high colonic expression of TNF-α, IL-1 α, IL-1β, IL-12, IFN-γ, IL-10, MIP-1α and KC. DSS concentrations as low as 0.5% were enough to induce bleeding, ulceration and weight loss in VDR KO mice. VDR KO mice failed to recover following the removal of DSS, while WT mice showed signs of recovery within 5 days of DSS removal. The early mortality of DSS treated VDR KO mice was likely due to perforation of the bowel and resulting endotoxemia. VDR KO mice were hyper-responsive to exogenously injected LPS and cultures of the peritoneal exudates of moribund DSS treated VDR KO mice were positive for bacterial growth. 1,25(OH)₂D₃ in the diet or rectally decreased the severity and extent of DSS-induced inflammation in WT mice.

Conclusion

The data point to a critical role for the VDR and 1,25(OH)₂D₃ in control of innate immunity and the response of the colon to chemical injury.