Induction of arginase I transcription by IL-4 requires a composite DNA response element for STAT6 and C/EBPβ

被引：149

作者：

Gray, MJ ^{[1
]}

Poljakovic, M ^{[1
]}

Kepka-Lenhart, D ^{[1
]}

Morris, SM ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA

来源：

GENE | 2005年 / 353卷 / 01期

关键词：

macrophage; nitric oxide; gene regulation; inflammation;

D O I：

10.1016/j.gene.2005.04.004

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Arginine metabolism-in macrophages during infection and inflammation is complex, owing to differential regulation of inducible nitric oxide synthase (iNOS) and arginases by cytokines and other agents. Changes in levels of Th2 cytokines such as interleukin-4 (IL-4) can play important roles in these conditions via effects on arginine metabolism. IL-4 alters macrophage arginine metabolism by inducing arginase I expression and inhibiting nitric oxide production. To determine the molecular basis for induction of arginase 1, the promoter of the murine arginase I gene was cloned and analyzed by transfection in RAW 264.7 macrophage cells. IL-4 induction required a composite response element containing STAT6 and C/EBP sites located 2.86 kb upstream of the transcription start site. Competition experiments showed that STAT6 and C/EBP bind to the STAT6 and C/EBP sites non cooperatively. Elucidation of the mechanisms involved in regulation of arginase I transcription may provide a basis for developing strategies to modulate arginase expression in Th2 cytokine-predominant diseases. (c) 2005 Elsevier B.V. All rights reserved.

引用

页码：98 / 106

页数：9

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