Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease

van Heel, David A, Ghosh, Subrata, Butler, Matt, Hunt, Karen A, Lundberg, Anna M C, Ahmad, Tariq, McGovern, Dermot P B, Onnie, Clive, Negoro, Kenichi, Goldthorpe, Sue, Foxwell, Brian M J, Mathew, Christopher G, Forbes, Alastair, Jewell, Derek P and Playford, Raymond J (2005) Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease. Lancet, 365 (9473). pp. 1794-1796. ISSN 0140-6736

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Abstract

Both NOD2 (CARD15) alleles are mutated in roughly 15% of patients with Crohn's disease, but functional effects are unclear. We analysed the cytokine response of peripheral blood mononuclear cells to muramyl dipeptide (MDP), the ligand for NOD2. MDP induced little TNFalpha or interleukin 1beta, but strong interleukin-8 secretion. MDP also substantially upregulated secretion of TNFalpha and interleukin 1beta induced by toll-like receptor ligands. These effects were abolished by the most common Crohn's NOD2 double mutant genotypes at low nanomolar MDP concentrations, and provide the basis to develop a test of NOD2 functional deficiency. In Crohn's disease, there are defects in neutrophil recruitment driven by NOD2 and interleukin 8 and in cross talk between the NOD2 and toll-like receptor pathways, which suggests that the immune system fails to receive an early priming signal.

Item Type: Article
Uncontrolled Keywords: acetylmuramyl-alanyl-isoglutamine,crohn disease,genotype,humans,immunity, innate,interleukin-1,interleukin-8,intracellular signaling peptides and proteins,leukocytes, mononuclear,membrane glycoproteins,mutation,nod2 signaling adaptor protein,receptor cross-talk,receptors, cell surface,signal transduction,toll-like receptors,tumor necrosis factor-alpha,up-regulation
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Nutrition
Depositing User: Pure Connector
Date Deposited: 06 Aug 2014 11:58
Last Modified: 23 Aug 2018 14:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/49634
DOI: 10.1016/S0140-6736(05)66582-8

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