Enhancer-Mediated Control of Macrophage-Specific Arginase I Expression

  • Anne-Laure Pauleau
    Department of Infectious Diseases, St. Jude Children’s Research Hospital , Memphis, TN 38105
  • Robert Rutschman
    Department of Infectious Diseases, St. Jude Children’s Research Hospital , Memphis, TN 38105
  • Roland Lang
    Department of Infectious Diseases, St. Jude Children’s Research Hospital , Memphis, TN 38105
  • Alessandra Pernis
    Department of Medicine, Columbia University , New York, NY 10032
  • Stephanie S Watowich
    Department of Immunology, M. D. Anderson Cancer Center , Houston, TX 77030
  • Peter J Murray
    Department of Infectious Diseases, St. Jude Children’s Research Hospital , Memphis, TN 38105

書誌事項

公開日
2004-06
権利情報
  • https://academic.oup.com/pages/standard-publication-reuse-rights
DOI
  • 10.4049/jimmunol.172.12.7565
公開者
Oxford University Press (OUP)

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説明

<jats:title>Abstract</jats:title> <jats:p>Arginase I expression in the liver must remain constant throughout life to eliminate excess nitrogen via the urea cycle. In contrast, arginase I expression in macrophages is silent until signals from Th2 cytokines such as IL-4 and IL-13 are received and the mRNA is then induced four to five orders of magnitude. Arginase I is hypothesized to play a regulatory and potentially pathogenic role in diseases such as asthma, parasitic, bacterial, and worm infections by modulating NO levels and promoting fibrosis. We show that Th2-inducible arginase I expression in mouse macrophages is controlled by an enhancer that lies −3 kb from the basal promoter. PU.1, IL-4-induced STAT6, and C/EBPβ assemble at the enhancer and await the effect of another STAT6-regulated protein(s) that must be synthesized de novo. Identification of a powerful extrahepatic regulatory enhancer for arginase I provides potential to manipulate arginase I activity in immune cells while sparing liver urea cycle function.</jats:p>

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