Inflammatory bowl diseaseHow does vitamin D work?

Vitamin D has several mechanisms whereby it reduces the risk of Crohn’s disease (CD).

One is that it regulates the T-helper 1 (Th1) to Th2 balance towards Th2, which generates cytokines that are less proinflammatory including reduced tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in systemic inflammation1.

Another recent paper identified a role for 1,25-dihydroxyvitamin D in affecting expression of the NOD2 gene both directly and indirectly though effects on NF-kB:

Variants in the NOD2/CARD15/IBD1 locus are associated with the strongest risk of development of CD2. NOD2 encodes a protein that is a member of a family of intracellular pattern recognition receptors3. NOD2 recog-nizes modified forms of muramyl didpeptide (MDP), a lysosomal breakdown product of bacterial peptidoglycan. Recent work by one of our team has shown that NOD2 is particularly sensitive to the N-glycolyl form of MDP produced by mycobacteria4. 

Recently our group found that transcription of the NOD2 gene was stimulated directly by the 1,25D-bound VDR. Regulation of NOD2 expression by 1,25D is noteworthy for several reasons. Signaling through NOD2 induces the function of the NF-kB transcription factor, which in turn induces expression of DEFB2/HBD256.

Page last edited: 06 May 2011

References

  1. Ardizzone, S. Cassinotti, A. Trabattoni, D. Manzionna, G. Rainone, V. Bevilacqua, M. Massari, A. Manes, G. Maconi, G. Clerici, M. Bianchi Porro, G. Immunomodulatory effects of 1,25-dihydroxyvitamin D3 on TH1/TH2 cytokines in inflammatory bowel disease: an in vitro study. Int J Immunopathol Pharmacol. 2009 Jan-Mar; 22 (1): 63-71.
  2. Hugot, J. P. Chamaillard, M. Zouali, H. Lesage, S. Cezard, J. P. Belaiche, J. Almer, S. Tysk, C. O’Morain, C. A. Gassull, M. Binder, V. Finkel, Y. Cortot, A. Modigliani, R. Laurent-Puig, P. Gower-Rousseau, C. Macry, J. Colombel, J. F. Sahbatou, M. Thomas, G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001 May 31; 411 (6837): 599-603.
  3. Inohara, N. Ogura, Y. Fontalba, A. Gutierrez, O. Pons, F. Crespo, J. Fukase, K. Inamura, S. Kusumoto, S. Hashimoto, M. Foster, S. J. Moran, A. P. Fernandez-Luna, J. L. Nunez, G. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem. 2003 Feb 21; 278 (8): 5509-12.
  4. Coulombe, F. Divangahi, M. Veyrier, F. de Leseleuc, L. Gleason, J. L. Yang, Y. Kelliher, M. A. Pandey, A. K. Sassetti, C. M. Reed, M. B. Behr, M. A. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J Exp Med. 2009 Aug 3; 206 (8): 1709-16.
  5. Wang, T. T. Dabbas, B. Laperriere, D. Bitton, A. J. Soualhine, H. Tavera-Mendoza, L. E. Dionne, S. Servant, M. J. Bitton, A. Seidman, E. G. Mader, S. Behr, M. A. White, J. H. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010 Jan 22; 285 (4): 2227-31.
  6. Verway, M. Behr, M. A. White, J. H. Vitamin D, NOD2, autophagy and Crohn’s disease. Expert Rev Clin Immunol. 2010 Jul; 6 (4): 505-8.