Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
J Immunol ; 166(4): 2173-7, 2001 Feb 15.
Article in English | MEDLINE | ID: mdl-11160269

ABSTRACT

The cytokines IL-4 and IL-13 inhibit the production of NO from activated macrophages through an unresolved molecular mechanism. We show here that IL-4 and IL-13 regulate NO production through depletion of arginine, the substrate of inducible NO synthase (iNOS). Inhibition of NO production from murine macrophages stimulated with LPS and IFN-gamma by IL-4 or IL-13 was dependent on Stat6, cell density in the cultures, and pretreatment for at least 6 h. IL-4/IL-13 did not interfere with the expression or activity of iNOS but up-regulated arginase I (the liver isoform of arginase) in a Stat6-dependent manner. Addition of exogenous arginine completely restored NO production in IL-4-treated macrophages. Furthermore, impaired killing of the intracellular pathogen Toxoplasma gondii in IL-4-treated macrophages was overcome by supplementing L-arginine. The simple system of regulated substrate competition between arginase and iNOS has implications for understanding the physiological regulation of NO production.


Subject(s)
Nitric Oxide/biosynthesis , Trans-Activators/physiology , Animals , Arginase/biosynthesis , Arginine/deficiency , Cells, Cultured , Down-Regulation/immunology , Interleukin-13/physiology , Interleukin-4/physiology , Macrophage Activation , Macrophages, Peritoneal/enzymology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/parasitology , Mice , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , STAT6 Transcription Factor , Substrate Specificity/immunology , Toxoplasmosis, Animal/enzymology , Toxoplasmosis, Animal/immunology , Toxoplasmosis, Animal/metabolism , Trans-Activators/deficiency , Trans-Activators/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...