First Author | Hurgin V | Year | 2007 |
Journal | Proc Natl Acad Sci U S A | Volume | 104 |
Issue | 12 | Pages | 5044-9 |
PubMed ID | 17360358 | Mgi Jnum | J:120091 |
Mgi Id | MGI:3703847 | Doi | 10.1073/pnas.0611608104 |
Citation | Hurgin V, et al. (2007) Antiviral and immunoregulatory activities of IFN-gamma depend on constitutively expressed IL-1alpha. Proc Natl Acad Sci U S A 104(12):5044-9 |
abstractText | IFN-gamma induces its immunoregulatory activities by activating genes mainly through the Jak-STAT signaling pathway. Here we show that what was considered to be intrinsic IFN-gamma activities depend largely on the basal level of NF-kappaB, which is maintained by constitutively expressed IL-1alpha. The IL-1 receptor antagonist and antibodies to IL-1alpha, but not to IL-1beta, inhibited the antiviral activity of IFN-gamma by 90%, whereas no inhibition of type I IFN activity was observed. Similarly, the induction of many genes by IFN-gamma, including HLA-DR, ICAM-1, IL-18BP, and genes mediating its antiviral activity, greatly depended on basal IL-1alpha. Furthermore, IFN-gamma induced serum IL-18 binding protein in wild-type mice but not in IL-1alpha/beta double-deficient mice. Thus, constitutively expressed IL-1alpha is critical for numerous IFN-gamma activities. |