The Lancet (British edition), 2005-05, Vol.365 (9473), p.1794-1796
2005
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease
- Ist Teil von
- The Lancet (British edition), 2005-05, Vol.365 (9473), p.1794-1796
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2005
- Quelle
- Business Source Ultimate【Trial: -2024/12/31】【Remote access available】
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0140-6736eISSN: 1474-547XDOI: 10.1016/S0140-6736(05)66582-8Titel-ID: cdi_proquest_miscellaneous_67857602
- Format
- –
- Schlagworte
- Acetylmuramyl-Alanyl-Isoglutamine - metabolism, Acetylmuramyl-Alanyl-Isoglutamine - pharmacology, Crohn Disease - genetics, Crohn Disease - immunology, Crohn Disease - metabolism, Crohns disease, Cytokines, Genotype, Genotype & phenotype, Genotypes, Humans, Immune system, Immunity, Innate, In Vitro Techniques, Interleukin-1 - biosynthesis, Interleukin-1 - metabolism, Interleukin-8 - biosynthesis, Interleukin-8 - metabolism, Intracellular Signaling Peptides and Proteins - genetics, Intracellular Signaling Peptides and Proteins - metabolism, Leukocytes, Mononuclear - metabolism, Membrane Glycoproteins - metabolism, Mutation, Nod2 Signaling Adaptor Protein, Peptides, Receptor Cross-Talk, Receptors, Cell Surface - metabolism, Signal Transduction, Toll-Like Receptors, Tumor Necrosis Factor-alpha - biosynthesis, Tumor Necrosis Factor-alpha - metabolism, Up-Regulation