Anti-inflammatory action of type I interferons deduced from mice expressing interferon β

L. Boscá, O. G. Bodelón, S. Hortelano, A. Casellas, F. Bosch

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Abstract

Type I interferons (IFN) are widely used for the therapeutic treatment of viral infections, tumor growth and various chronic diseases such as multiple sclerosis. Antagonism between type I IFNs and IFN-γ has been described in cells of the immune system, in particular in the activation of macrophages. To study the systemic effects of type I IFNs we used transgenic mice carrying a human IFN-β (hIFN-β gene under the control of the rat insulin I promoter. These animals expressed high levels of hIFN-β in β-pancreatic cells, and the ability of the macrophages to respond to proinflammatory stimuli was analyzed. Transgenic mice exhibited an increased extravasation of cells to the peritoneal cavity after eliciting with thioglycollate broth. The expression of the inducible form of nitric oxide synthase and cyclooxygenase-2, two enzymes involved in inflammation, was impaired in transgenic animals challenged with lipopolysaccharide and IFN-γ. Analysis of the mechanisms leading to this attenuated inflammatory response showed a decrease in the serum levels of TNF-α and an inhibition of the activation of the transcription factor NF-κB in various tissues. These results indicate that systemic administration of IFN-β might influence the response to pro-inflammatory stimuli, in particular through the antagonism of IFN-γ signaling.
Original languageEnglish
Pages (from-to)817-825
JournalGene Therapy
Volume7
Issue number10
DOIs
Publication statusPublished - 1 Jan 2000

Keywords

  • Interferon β
  • Macrophage
  • Nitric oxide
  • Nuclear factor κB
  • Transgenic mice

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    Boscá, L., Bodelón, O. G., Hortelano, S., Casellas, A., & Bosch, F. (2000). Anti-inflammatory action of type I interferons deduced from mice expressing interferon β. Gene Therapy, 7(10), 817-825. https://doi.org/10.1038/sj.gt.3301179