Abstract Activated macrophages avidly consume arginine via the action of inducible nitric oxide synthase (iNOS) and/or arginase. In contrast to our knowledge regarding macrophage iNOS expression, the stimuli and mechanisms that regulate expression of the cytosolic type I (arginase I) or mitochondrial type II (arginase II) isoforms of arginase in macrophages are poorly defined. We show that one or both arginase isoforms may be induced in the RAW 264.7 murine macrophage cell line and that arginase expression is regulated independently of iNOS expression. For example, 8-bromo-cAMP strongly induced both arginase I and II mRNAs but not iNOS. Whereas interferon-γ induced iNOS but not arginase, 8-bromo-cAMP and interferon-γ mutually antagonized induction of iNOS and arginase I mRNAs. Dexamethasone, which did not induce either arginase or iNOS, almost completely abolished induction of arginase I mRNA by 8-bromo-cAMP but enhanced induction of arginase II mRNA. Lipopolysaccharide (LPS) induced arginase II mRNA, but 8-bromo-cAMP plus LPS resulted in synergistic induction of both arginase I and II mRNAs. In all cases, increases in arginase mRNAs were sufficient to account for the increases in arginase activity. These complex patterns of expression suggest that the arginase isoforms may play distinct, although partially overlapping, functional roles in macrophage arginine metabolism. arginine adenosine 3′,5′-cyclic monophosphate interferon-γ lipopolysaccharide Footnotes Address for reprint requests: S. M. Morris, Jr., Dept. of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261. This work was supported in part by National Institute of General Medical Sciences Grants RO1 GM-50897, RO1 GM-57384, and T32 GM-08516. Current address of L.-C. Chen: Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1998 the American Physiological Society
AJP - Endocrinology and Metabolism – The American Physiological Society
Published: Nov 1, 1998
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