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Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1

Genes & Immunity volume 5, pages 26–35 (2004)Cite this article

Abstract

The genes of the transporter associated with antigen processing (Tap)-1, and the low molecular weight peptide (Lmp)-2, are crucial for class I major histocompatibility complex function and share a common bidirectional promoter. In murine bone marrow-derived macrophages, interferon gamma (IFN-γ) induced Tap-1 and upregulated Lmp-2, which is constitutively expressed at low levels. The IFN-γ-induction was independent of early gene synthesis. The mRNA induced by IFN-γ was very stable. In macrophages from STAT1 knockout mice, IFN-γ did not induce the expression of Tap-1 or Lmp-2. Several areas in the promoter can be controlled by IFN-γ, such as proximal and distal GAS boxes in the direction of the Tap-1 gene, NFγB and IRF-1 boxes. By making deletions of the promoter, we found that only the proximal GAS and IRF-1 boxes are required for IFN-γ induction of Tap-1 and Lmp-2. Experiments using nuclear extracts from macrophages treated for 30 min with IFN-γ and gel shift analysis indicated that STAT1 binds to the GAS box. The nuclear extracts from macrophages treated for at least 2 h with IFN-γ bound to the IRF-1 box. These results indicate that both STAT1 and IRF-1 are required for the IFN-γ induction of Tap-1 and Lmp-2 genes.

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Acknowledgements

We thank Dr Robert D Schreiber for the gift of bone marrow-derived macrophages from the STAT1 KO mice and Tanya Yates for editing the manuscript. AC was supported by grants from the Ministerio de Ciencia y Tecnología (BMC2001-3040) and the Fundació la Marató de TV3 (1010).

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Author notes

  1. M Brucet, L Marqués, J Lloberas and A Celada: The first two and the last two authors contributed equally to this work.

Authors and Affiliations

  1. Group of Macrophage Biology, Institute of Biomedical Research of Barcelona, Barcelona Science Park, University of Barcelona, Spain

    M Brucet, L Marqués, C Sebastián, J Lloberas & A Celada

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  1. M Brucet
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  2. L Marqués
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Correspondence to A Celada.

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Brucet, M., Marqués, L., Sebastián, C. et al. Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1. Genes Immun 5, 26–35 (2004). https://doi.org/10.1038/sj.gene.6364035

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