The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages.

The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. Research Abstract Details 

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The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. Abstract Text:

Chaitra Marathe,Michelle N Bradley,Cynthia Hong,Felix Lopez,Carlos M Ruiz de Galarreta,Peter Tontonoz,Antonio Castrillo,

The liver X receptors (LXRs) are ligand-dependent transcription factors that have been implicated in lipid metabolism and inflammation. LXRs also inhibit the expression of inflammatory genes in macrophages, including inducible nitric oxide synthase (iNOS). Some of these actions are mediated through LXR antagonism of NF-kappaB activity. The potential for LXRs to positively regulate the expression of anti-inflammatory molecules, however, has not been explored. Here we show that the arginase II (ArgII) gene is a direct target for LXR regulation. ArgII catalyzes the conversion of L-arginine into L-ornithine and urea, leading to the synthesis of polyamines. Expression of ArgII is induced by LXR agonists in macrophage cell lines and primary murine macrophages in a receptor-dependent manner. The ArgII promoter contains a functional LXR response elements that mediates promoter induction by LXR/RXR (retinoid X receptor) in transfection assays. Since ArgII and iNOS utilize a common substrate, induction of ArgII expression has the potential to exert anti-inflammatory effects by shifting arginine metabolism toward polyamine synthesis at the expense of NO production. In support of this hypothesis, we demonstrate that forced expression of ArgII mimics the inhibitory effect of LXR activation on macrophage NO production. Furthermore, inhibition of arginase activity partially reverses the inhibitory effect of LXR agonists on NO production. These studies suggest that regulation of ArgII may contribute to the immunomodulatory effects of LXRs.

The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. Publishing Authors By Initials

C Marathe,MN Bradley,C Hong,F Lopez,CM Ruiz de Galarreta,P Tontonoz,A Castrillo,

For similar proteins: receptors, cytoplasmic and nuclear research abstracts see: proteins: receptors, cytoplasmic and nuclear research

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The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 32197-206

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 30

MONTH: 08

YEAR: 2006

The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. Keywords Mesh Terms:

KEYWORDS: Receptors, Cytoplasmic and Nuclear

MESH TERMS: metabolism

Chemical & Substance for Abstract: The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. Information

Substance Name: Arginase

Registry Number: EC 3.5.3.1

Grant and Affiliation Information for The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages.

AFFILIATION: Howard Hughes Medical Institute, Molecular Biology Institute and Department of Pathology and Laboratory Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL 66088

ACRONYM: HL

MEDLINETA: J Biol Chem

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