Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.

Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Research Abstract Details 

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Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Abstract Text:

Junichiro Sonoda, ,Isaac R Mehl,Grant D Barish,Ling-Wa Chong,Xiangli Li,Immo E Scheffler,Dennis C Mock,Alain R Bataille,Francois Robert,Chih-Hao Lee,Vincent ,Ronald M Evans,

Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature of the IFN-gamma-induced activation pathway is not known. Here we show using genome-wide expression and chromatin-binding profiling that IFN-gamma induces the expression of many nuclear genes encoding mitochondrial respiratory chain machinery via activation of the nuclear receptor ERR alpha (estrogen-related receptor alpha, NR3B1). Studies with macrophages lacking ERR alpha demonstrate that it is required for induction of mitochondrial reactive oxygen species (ROS) production and efficient clearance of Listeria monocytogenes (LM) in response to IFN-gamma. As a result, mice lacking ERR alpha are susceptible to LM infection, a phenotype that is localized to bone marrow-derived cells. Furthermore, we found that IFN-gamma-induced activation of ERR alpha depends on coactivator PGC-1 beta (peroxisome proliferator-activated receptor gamma coactivator-1 beta), which appears to be a direct target for the IFN-gamma/STAT-1 signaling cascade. Thus, ERR alpha and PGC-1 beta act together as a key effector of IFN-gamma-induced mitochondrial ROS production and host defense.

Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Publishing Authors By Initials

J Sonoda,J ,IR Mehl,GD Barish,LW Chong,X Li,IE Scheffler,DC Mock,AR Bataille,F Robert,CH Lee,V ,RM Evans,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Genes & development

VOLUME: 21

Page Numbers: 1909-20

Journal Abbreviation: Genes Dev.

ISSN: 0890-9369

DAY: 1

MONTH: Aug

YEAR: 2007

Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Information

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LANGUAGE: eng

NlmUniqueID: 8711660

Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: drug effects

Chemical & Substance for Abstract: Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.

AFFILIATION: Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: U19 DK62434-01

ACRONYM: DK

MEDLINETA: Genes Dev

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