| First Author | Sheikh SZ | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 8 | Pages | 4069-73 |
| PubMed ID | 20228197 | Mgi Jnum | J:159881 |
| Mgi Id | MGI:4452583 | Doi | 10.4049/jimmunol.0903600 |
| Citation | Sheikh SZ, et al. (2010) Cutting edge: IFN-gamma is a negative regulator of IL-23 in murine macrophages and experimental colitis. J Immunol 184(8):4069-73 |
| abstractText | IL-23 regulation is a central event in the pathogenesis of the inflammatory bowel diseases. We demonstrate that IFN-gamma has anti-inflammatory properties in the initiation phase of IL-23-mediated experimental colitis. IFN-gamma attenuates LPS-mediated IL-23 expression in murine macrophages. Mechanistically, IFN-gamma inhibits Il23a promoter activation through altering NF-kappaB binding and histone modification. Moreover, intestinal inflammation is inhibited by IFN-gamma signaling through attenuation of Il23a gene expression. In germ-free wild-type mice colonized with enteric microbiota, inhibition of colonic Il23a temporally correlates with induction of IFN-gamma. IFN-gammaR1/IL-10 double-deficient mice demonstrate markedly increased colonic inflammation and IL23a expression compared with those of IL-10(-/-) mice. Colonic CD11b(+) cells are the primary source of IL-23 and a target for IFN-gamma. This study describes an important anti-inflammatory role for IFN-gamma through inhibition of IL-23. Converging genetic and functional findings suggest that IL-23 and IFN-gamma are important pathogenic molecules in human inflammatory bowel disease. |
