Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing
Journal
Science
Journal Volume
307
Journal Issue
5710
Pages
734-783
Date Issued
2005-02-04
Author(s)
Maeda, Shin
Liu, Hongjun
Bankston, Laurie A
Iimura, Mitsutoshi
Kagnoff, Martin F
Eckmann, Lars
Karin, Michael
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.
SDGs
Publisher
American Association for the Advancement of Science
Type
journal article