| First Author | Warner N | Year | 2013 |
| Journal | Sci Signal | Volume | 6 |
| Issue | 258 | Pages | rs3 |
| PubMed ID | 23322906 | Mgi Jnum | J:259506 |
| Mgi Id | MGI:6141347 | Doi | 10.1126/scisignal.2003305 |
| Citation | Warner N, et al. (2013) A genome-wide siRNA screen reveals positive and negative regulators of the NOD2 and NF-kappaB signaling pathways. Sci Signal 6(258):rs3 |
| abstractText | The cytoplasmic receptor NOD2 (nucleotide-binding oligomerization domain 2) senses peptidoglycan fragments and triggers host defense pathways, including activation of nuclear factor kappaB (NF-kappaB) signaling, which lead to inflammatory immune responses. Dysregulation of NOD2 signaling is associated with inflammatory diseases, such as Crohn''s disease and Blau syndrome. We used a genome-wide small interfering RNA screen to identify regulators of the NOD2 signaling pathway. Several genes associated with Crohn''s disease risk were identified in the screen. A comparison of candidates from this screen with other "omics" data sets revealed interconnected networks of genes implicated in NF-kappaB signaling, thus supporting a role for NOD2 and NF-kappaB pathways in the pathogenesis of Crohn''s disease. Many of these regulators were validated in secondary assays, such as measurement of interleukin-8 secretion, which is partially dependent on NF-kappaB. Knockdown of putative regulators in human embryonic kidney 293 cells followed by stimulation with tumor necrosis factor-alpha revealed that most of the genes identified were general regulators of NF-kappaB signaling. Overall, the genes identified here provide a resource to facilitate the elucidation of the molecular mechanisms that regulate NOD2- and NF-kappaB-mediated inflammation. |
