| First Author | Fantuzzi G | Year | 2001 |
| Journal | Eur J Immunol | Volume | 31 |
| Issue | 2 | Pages | 369-75 |
| PubMed ID | 11180100 | Mgi Jnum | J:119157 |
| Mgi Id | MGI:3701386 | Doi | 10.1002/1521-4141(200102)31:2<369::aid-immu369>3.0.co;2-y |
| Citation | Fantuzzi G, et al. (2001) Role of interferon regulatory factor-1 in the regulation of IL-18 production and activity. Eur J Immunol 31(2):369-75 |
| abstractText | Interferon regulatory factor-1 (IRF-1) is a transcription factor regulating the expression of several cytokines. Using IRF-1 knockout (KO) mice, the role of IRF-1 in the production and activity of IL-18 was evaluated. Administration of IL-12 or concanavalin A significantly increased levels of circulating IL-18 in wild-type (WT), but not in IRF-1 KO mice. However, despite these differences in circulating IL-18 levels, no or only minor differences in constitutive or inducible IL-18 mRNA and tissue-associated protein levels were observed between WT and IRF-1 KO mice. On the other hand, we observed that constitutive and inducible levels of the IL-18-processing enzyme caspase-1 were markedly reduced in the spleen and the liver of IRF-1 KO compared to WT mice. In addition, both constitutive and inducible liver mRNA levels for the IL-18 binding protein (IL-18BP), a specific IL-18 antagonist, were significantly lower in IRF-1 KO than in WT mice. Compared to IL-12, IL-18 only weakly induced IRF-1 mRNA in cultured splenocytes. However, IL-18-induced IFN-gamma production was strongly reduced in splenocytes from IRF-1 KO compared to WT cells. In conclusion, IRF-1 regulates IL-18 production and activity mostly by modulating expression of caspase-1 and IL-18BP. In addition, IRF-1 participates in the induction of IFN-gamma by IL-18. |
