HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, J. Articles by Gu, J. Search for Related Content PubMed PubMed Citation Articles by Wang, J. Articles by Gu, J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH

Retinoic Acid-Inducible Gene-I Mediates Late Phase Induction of TNF- by Lipopolysaccharide¹

Jing Wang^2,*, Su Wu^2,*, Xin Jin^*, Mingtao Li, Shiyong Chen^*, Jessica L. Teeling, V. Hugh Perry and Jun Gu^3,*

^* National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing; Department of Pharmacology, SunYat-sen University, Guangzhou, China; and Central Nervous System Inflammation Group, School of Biological Sciences, University of Southampton, Southampton, United Kingdom

LPS is the known component of bacterial pathogens that stimulates a number of proinflammatory factors. However, the mechanism of the induction of these factors by LPS has not been fully elucidated. We show here that LPS induces retinoic acid-inducible gene-I (RIG-I) in vitro and in vivo as a result from autocrine secretion of IFN-β in macrophages. TIR-domain-containing adapter-inducing IFN-β-deficient mouse embryo fibroblast (trif^–/–) fail to show expression of RIG-I following LPS stimulation. Interference of RIG-I expression short interfering RNA represses the expression of LPS-induced TNF-, whereas over-expression of RIG-I leads to the activation of TNF- promoter and the induction of TNF- expression. LPS- and IFN-β-induced TNF- are suppressed in RIG-I-deficient mouse embryo fibroblasts (rig^–/–). Thus, RIG-I plays a key role in the expression of TNF- in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants 30330260 and 30470841 from National Science Foundation, Grant 2006CB503802 from National Basic Research Program, China, and by China Scholarship Programs.

² J.W. and S.W. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Jun Gu, Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China. E-mail address: gj{at}pku.edu.cn

⁴ Abbreviations used in this paper: RIG-I, retinoic acid-inducible gene-I; MEF, mouse embryo fibroblast; TRIF, TIR-domain-containing adapter-inducing IFN-β; CARD, caspase recruit domain; WT, wild type; siRNA, short interfering RNA; IRG, IFN-β response gene.