TY - JOUR
T1 - Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease
AU - Van Heel, David A.
AU - Ghosh, Subrata
AU - Butler, Matt
AU - Hunt, Karen A.
AU - Lundberg, Anna M.C.
AU - Ahmad, Tariq
AU - McGovern, Dermot P.B.
AU - Onnie, Clive
AU - Negoro, Kenichi
AU - Goldthorpe, Sue
AU - Foxwell, Brian M.J.
AU - Mathew, Christopher G.
AU - Forbes, Alastair
AU - Jewell, Derek P.
AU - Playford, Raymond J.
PY - 2005/5/21
Y1 - 2005/5/21
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/21144468350
U2 - 10.1016/S0140-6736(05)66582-8
DO - 10.1016/S0140-6736(05)66582-8
M3 - Article
C2 - 15910952
AN - SCOPUS:21144468350
SN - 0140-6736
VL - 365
SP - 1794
EP - 1796
JO - The Lancet
JF - The Lancet
IS - 9473
ER -