| First Author | Hu X | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 1 | Pages | 131-8 |
| PubMed ID | 15972639 | Mgi Jnum | J:100616 |
| Mgi Id | MGI:3588937 | Doi | 10.4049/jimmunol.175.1.131 |
| Citation | Hu X, et al. (2005) Homeostatic role of interferons conferred by inhibition of IL-1-mediated inflammation and tissue destruction. J Immunol 175(1):131-8 |
| abstractText | In addition to their well known immune and proinflammatory activities, IFNs possess homeostatic functions that limit inflammation and tissue destruction in a variety of conditions such as arthritis, osteolysis, and multiple sclerosis. The mechanisms underlying the homeostatic actions of IFNs are not well understood. We report here that both type I and type II IFNs (IFN-alpha, IFN-beta, and IFN-gamma, respectively) suppressed a broad range of proinflammatory and tissue-destructive activities of IL-1, including induction of inflammatory mediators, production of matrix metalloproteinases, macrophage tissue invasion, and cartilage degradation. IFN-alpha attenuated IL-1-mediated cell recruitment in vivo. IFNs completely suppressed the activation of IL-1 signal transduction pathways in macrophages. The mechanism of IFN-mediated inhibition of IL-1 action and signaling was modulation of IL-1R expression, which was also observed in vivo. IFN-gamma-mediated down-regulation of IL-1R type I expression was dependent on Stat1, a transcription factor typically considered to be a key mediator of macrophage activation by IFNs. These results identify cellular and molecular mechanisms that contribute to the homeostatic role of IFNs in limiting inflammation and associated tissue destruction. |
