The cytokine IL-1β activates IFN response factor 3 in human fetal astrocytes in culture

Mark A. Rivieccio, Gareth R. John, Xianyuan Song, Hyeon Sook Suh, Yongmei Zhao, Sunhee C. Lee, Celia F. Brosnan

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49 Scopus citations

Abstract

The cytokine IL-1β is a major activator of primary human fetal astrocytes in culture, leading to the production of a wide range of cytokines and chemokines important in the host defense against pathogens. IL-β, like TLR4, signals via the MyD88/IL-1βR-associated kinase-1 pathway linked to activation of NF-κB and AP-1. Recent studies have shown that TLR4 also signals independently of MyD88, resulting in the activation of IFN regulatory factor 3 (IRF3), a transcription factor required for the production of primary antiviral response genes such as IFN-β. Using a functional genomics approach, we observed that IL-β induced in astrocytes a group of genes considered to be IFN-stimulated genes (ISG), suggesting that IL-1β may also signal via IRF3 in these cells. We now show, using real-time PCR, that in astrocytes IL-1β induces the expression of IFN-β, IRF7, CXCL10/IFN-γ-inducible protein-10 and CCL5/RANTES. Chemokine expression was confirmed by ELISA. We also show that IL-1β induces phosphorylation and nuclear translocation of IRF3 and delayed phosphorylation of STAT1. The dependency of IFN-β, IRF7, and CXCL10/IFN-γ-inducible protein-10 gene expression on IRF3 was confirmed using a dominant negative IRF3-expressing adenovirus. The robust induction by IL-1β of additional ISG noted on the microarrays, such as STAT1, 2′5′-oligoadenylate synthetase 2, and ISG15, also supports an active signaling role for IL-1β via this pathway in human fetal astrocytes. These data are the first to show that IL-1β, in addition to TLRs, can stimulate IRF3, implicating this cytokine as an activator of genes involved in innate antiviral responses in astrocytes.

Original languageEnglish (US)
Pages (from-to)3719-3726
Number of pages8
JournalJournal of Immunology
Volume174
Issue number6
StatePublished - Mar 15 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rivieccio, M. A., John, G. R., Song, X., Suh, H. S., Zhao, Y., Lee, S. C., & Brosnan, C. F. (2005). The cytokine IL-1β activates IFN response factor 3 in human fetal astrocytes in culture. Journal of Immunology, 174(6), 3719-3726.