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


van Heel, DA and Ghosh, S and Butler, M and Hunt, KA and Lundberg, AMC and Ahmad, T and McGovern, DPB and Onnie, C and Negoro, K and Goldthorpe, S and Foxwell, BMJ and Mathew, CG and Forbes, A and Jewell, DP and Playford, RJ, Murarnyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease, The Lancet, 365, (9473) pp. 1794-1796. ISSN 0140-6736 (2005) [Refereed Article]

DOI: doi:10.1016/S0140-6736(05)66582-8


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 TNFα or interleukin 1β, but strong interleukin-8 secretion. MDP also substantially upregulated secretion of TNFα and interleukin 1β 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 Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Gastroenterology and hepatology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Playford, RJ (Professor Ray Playford)
ID Code:72939
Year Published:2005
Web of Science® Times Cited:261
Deposited By:Research Division
Deposited On:2011-09-05
Last Modified:2011-09-05

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