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Orphan Nuclear Receptor ERR alpha Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation

Title
Orphan Nuclear Receptor ERR alpha Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation
Author
양철수
Keywords
NF-KAPPA-B; ESTROGEN-RELATED RECEPTOR; TOLL-LIKE RECEPTORS; FATTY-ACID OXIDATION; POSTTRANSLATIONAL MODIFICATIONS; CELL-ACTIVATION; SIRTUIN 1; ENERGY; CANCER; ENZYME
Issue Date
2015-07
Publisher
CELL PRESS
Citation
IMMUNITY, v. 43, NO 1, Page. 80-91
Abstract
The orphan nuclear receptor estrogen-related receptor alpha (ERR alpha; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRa negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERR alpha-deficient (Esrra(-/-)) mice showed increased susceptibility to endo-toxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERR alpha regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERR alpha was required for the regulation of NF-kappa B signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERR alpha as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming.
URI
http://www.sciencedirect.com/science/article/pii/S1074761315002708http://hdl.handle.net/20.500.11754/26096
ISSN
1074-7613; 1097-4180
DOI
10.1016/j.immuni.2015.07.003
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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