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Science. 2005 Feb 4;307(5710):734-8.

Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing.

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1
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0723, USA.

Erratum in

  • Science. 2011 Jul 15;333(6040):288.
  • Science. 2005 Apr 29;308(5722):633.

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.

Comment in

PMID:
15692052
DOI:
10.1126/science.1103685
[Indexed for MEDLINE]
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