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Enhancer-mediated control of macrophage-specific arginase I expression.

Authors
  • Pauleau, Anne-Laure
  • Rutschman, Robert
  • Lang, Roland
  • Pernis, Alessandra
  • Watowich, Stephanie S
  • Murray, Peter J
Type
Published Article
Journal
Journal of immunology (Baltimore, Md. : 1950)
Publication Date
Jun 15, 2004
Volume
172
Issue
12
Pages
7565–7573
Identifiers
PMID: 15187136
Source
Medline
License
Unknown

Abstract

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/EBPbeta 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.

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