Cellular and Molecular Life Sciences

, Volume 70, Issue 18, pp 3391–3404

Muramyl dipeptide responsive pathways in Crohn’s disease: from NOD2 and beyond

  • Mohammad Salem
  • Jakob Benedict Seidelin
  • Gerhard Rogler
  • Ole Haagen Nielsen
Review

DOI: 10.1007/s00018-012-1246-4

Cite this article as:
Salem, M., Seidelin, J.B., Rogler, G. et al. Cell. Mol. Life Sci. (2013) 70: 3391. doi:10.1007/s00018-012-1246-4

Abstract

Crohn’s disease (CD) is one of main disease entities under the umbrella term chronic inflammatory bowel disease. The etiology of CD involves alterations in genetic, microbiological, and immunological factors. This review is devoted to the role of the bacterial wall compound muramyl dipeptide (MDP) for the activation of inflammatory pathways involved in the pathogenesis of CD. The importance of this molecule is underscored by the fact that (1) MDP, which is found in most Gram-negative and -positive bacteria, is able to trigger several immunological responses in the intestinal system, and (2) that alterations in several mediators of the MDP response including—but not restricted to—nucleotide oligomerization domain 2 (NOD2) are associated with CD. The normalization of MDP signaling is one of several important factors that influence the intestinal inflammatory response, a fact which emphasizes the pathogenic importance of MDP signaling for the pathogenesis of CD. The important aspects of NOD2 and non-NOD2 mediated effects of MDP for the development of CD are highlighted, as well as how alterations in these pathways might translate into the development of new therapeutic strategies.

Keywords

ATG16L1AutophagyCrohn's disease (CD)Inflammatory bowel disease (IBD)Innate lymfoid cellsInflammasomeMuramyl dipeptide (MDP)NF-κBNucleotide oligomerization domain 2Paneth cellsPeptidoglycanToll-like receptor

Copyright information

© Springer Basel 2012

Authors and Affiliations

  • Mohammad Salem
    • 1
  • Jakob Benedict Seidelin
    • 1
    • 2
  • Gerhard Rogler
    • 3
  • Ole Haagen Nielsen
    • 1
  1. 1.Department of Gastroenterology D, Medical Section, Herlev HospitalUniversity of CopenhagenHerlevDenmark
  2. 2.Department of Internal Medicine, Bispebjerg HospitalUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of Gastroenterology and HepatologyZürich University HospitalZurichSwitzerland