| First Author | Maeda S | Year | 2005 |
| Journal | Science | Volume | 307 |
| Issue | 5710 | Pages | 734-8 |
| PubMed ID | 15692052 | Mgi Jnum | J:96128 |
| Mgi Id | MGI:3529429 | Doi | 10.1126/science.1103685 |
| Citation | Maeda S, et al. (2005) Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science 307(5710):734-8 |
| abstractText | 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. |
