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 B (NF-B) and antibacterial defenses, but Crohn's disease clinical specimens display elevated NF-B activity.
Dr Karin and colleagues from California, America undertook a study in order to illuminate the pathophysiological function of NOD2.
|Mutant mice exhibited elevated NF-B activation in response to muramyl dipeptide|
In order to do so, the research team introduced such a variant to the mouse Nod2 locus.
Dr Karin concluded, "We found that the mutant mice exhibited elevated NF-B activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1ß (IL-1ß)."
"These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-B activation and IL-1ß secretion."