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- How 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
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- 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.
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