Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease.
Lancet
; 365(9473): 1794-6, 2005.
Article
en En
| MEDLINE
| ID: mdl-15910952
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.
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Colección:
01-internacional
Asunto principal:
Glicoproteínas de Membrana
/
Transducción de Señal
/
Enfermedad de Crohn
/
Acetilmuramil-Alanil-Isoglutamina
/
Receptores de Superficie Celular
/
Péptidos y Proteínas de Señalización Intracelular
Tipo de estudio:
Diagnostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Lancet
Año:
2005
Tipo del documento:
Article
País de afiliación:
Reino Unido