Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation
| Autor: | Ki-Sun Park, Eun-Kyeong Jo, Jin-Man Kim, Vincent Giguère, Hye-Mi Lee, Tae Sung Kim, Hyo Sun Jin, Chul-Su Yang, Soo Yeon Kim, Jin Kyung Kim, Gi Ryang Kweon, Jean-Marc Vanacker, Catherine R. Dufour, Chul-Ho Lee, Jeongsu Han, Hueng-Sik Choi, David D. Moore, Jae-Min Yuk |
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| Přispěvatelé: | Chungnam National University (CNU), McGill University = Université McGill [Montréal, Canada], Hanyang University, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Chonnam National University, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Molecular and Cellular Biology, Baylor College of Medicine (BCM), Baylor University-Baylor University, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon) |
| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
Transcription Genetic [SDV]Life Sciences [q-bio] Immunology Regulator Inflammation Calcium-Calmodulin-Dependent Protein Kinase Kinase Oxidative Phosphorylation Estrogen-related receptor alpha Mice Sirtuin 1 medicine Animals Immunology and Allergy Respiratory function [INFO]Computer Science [cs] Receptor Promoter Regions Genetic Cells Cultured Tumor Necrosis Factor alpha-Induced Protein 3 Mice Knockout TNF Receptor-Associated Factor 6 biology Macrophages Intracellular Signaling Peptides and Proteins Transcription Factor RelA Ubiquitination Acetylation Hypoxia-Inducible Factor 1 alpha Subunit NAD Shock Septic Cell biology Enzyme Activation Toll-Like Receptor 4 Cysteine Endopeptidases Infectious Diseases Nuclear receptor Receptors Estrogen Myeloid Differentiation Factor 88 biology.protein Cancer research Calcium Signal transduction medicine.symptom Glycolysis Signal Transduction |
| Zdroj: | Immunity Immunity, 2015, 43 (1), pp.80-91. ⟨10.1016/j.immuni.2015.07.003⟩ Immunity, Elsevier, 2015, 43 (1), pp.80-91. ⟨10.1016/j.immuni.2015.07.003⟩ |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2015.07.003 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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