title: Muramyl dipeptide responsive pathways in Crohn's disease: from NOD2 and beyond.
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.
authors.affiliation: Department of Gastroenterology D, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Salem
authors.forename: Jakob Benedict
authors.initials: JB
authors.lastname: Seidelin
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D001692:Biological Transport; D003424:Crohn Disease / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007249:Inflammation; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D019879:Paneth Cells / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D051193:Toll-Like Receptors; D000119:Acetylmuramyl-Alanyl-Isoglutamine