| First Author | Hu X | Year | 2006 |
| Journal | Immunity | Volume | 24 |
| Issue | 5 | Pages | 563-74 |
| PubMed ID | 16713974 | Mgi Jnum | J:113359 |
| Mgi Id | MGI:3665513 | Doi | 10.1016/j.immuni.2006.02.014 |
| Citation | Hu X, et al. (2006) IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins. Immunity 24(5):563-74 |
| abstractText | The control of IL-10 production and mechanisms that mediate synergy between IFN-gamma and TLR ligands are not well understood. We report that IFN-gamma augments induction of TNFalpha by TLR ligands, immune complexes, and zymosan by suppressing IL-10 production and thereby interrupting Stat3-mediated feedback inhibition. IFN-gamma altered TLR2-induced signal transduction by increasing GSK3 activity and suppressing MAPK activation, leading to diminished IL-10 production. Inhibition of GSK3 or ablation of the GSK3beta gene ameliorated TLR2-induced peritonitis and arthritis. IFN-gamma suppressed the activity of CREB and AP-1, transcription factors that induce IL-10 expression and are regulated in part by MAPKs and GSK3. These results yield insight into mechanisms by which IFN-gamma regulates IL-10 production and TLR2-mediated inflammatory responses and identify inhibition of CREB and AP-1 as part of the macrophage response to IFN-gamma. GSK3 and CREB/AP-1 are key players in integrating IFN-gamma and TLR2 responses in innate immunity and inflammation. |
