Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing.
Science
; 307(5710): 734-8, 2005 Feb 04.
Article
en En
| MEDLINE
| ID: mdl-15692052
ABSTRACT
Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD). These variants are thought to be defective in activation of nuclear factor kappaB (NF-kappaB) and antibacterial defenses, but CD clinical specimens display elevated NF-kappaB activity. To illuminate the pathophysiological function of NOD2, we introduced such a variant to the mouse Nod2 locus. Mutant mice exhibited elevated NF-kappaB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1beta (IL-1beta). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Crohn
/
FN-kappa B
/
Interleucina-1
/
Colon
/
Péptidos y Proteínas de Señalización Intracelular
/
Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos