Arginase induction by suppressors of nitric oxide synthesis (IL-4, IL-10 and PGE2) in murine bone-marrow-derived macrophages

Biochem Biophys Res Commun. 1995 Jan 17;206(2):667-73. doi: 10.1006/bbrc.1995.1094.

Abstract

The present study addresses the regulatory mechanisms involved in the arginine metabolism of macrophages by arginase and nitric oxide synthase. Induction of both enzymes with LPS or by mixed lymphocyte reaction has been reported. Here, we demonstrate that these enzymes can be independently induced in murine bone-marrow-derived macrophages with the appropriate agonists. Arginase expression is specifically triggered by IL-4, IL-10, PGE2 as well as non-toxic or detoxified LPS. Conversely, IFN gamma induces only NO synthesis in these cells. The results demonstrate that the metabolism of arginine in macrophages is controlled by TH1/TH2-dependent cytokines and suggest a regulatory role of arginase on the NO synthesis by intracellular substrate depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Amino Acid Oxidoreductases / biosynthesis
  • Animals
  • Arginase / biosynthesis*
  • Bone Marrow Cells
  • Cells, Cultured
  • Dinoprostone / pharmacology*
  • Enzyme Induction
  • Interleukin-10 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide Synthase

Substances

  • Lipopolysaccharides
  • Interleukin-10
  • Interleukin-4
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Arginase
  • Dinoprostone