Dual Deletion of the Sirtuins SIRT2 and SIRT3 Impacts on Metabolism and Inflammatory Responses of Macrophages and Protects From Endotoxemia.

Details

Serval ID
serval:BIB_393C04540461
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dual Deletion of the Sirtuins SIRT2 and SIRT3 Impacts on Metabolism and Inflammatory Responses of Macrophages and Protects From Endotoxemia.
Journal
Frontiers in immunology
Author(s)
Heinonen T., Ciarlo E., Rigoni E., Regina J., Le Roy D., Roger T.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
10
Pages
2713
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Sirtuin 2 (SIRT2) and SIRT3 are cytoplasmic and mitochondrial NAD-dependent deacetylases. SIRT2 and SIRT3 target proteins involved in metabolic, proliferation and inflammation pathways and have been implicated in the pathogenesis of neurodegenerative, metabolic and oncologic disorders. Both pro- and anti-inflammatory effects have been attributed to SIRT2 and SIRT3, and single deficiency in SIRT2 or SIRT3 had minor or no impact on antimicrobial innate immune responses. Here, we generated a SIRT2/3 double deficient mouse line to study the interactions between SIRT2 and SIRT3. SIRT2/3 <sup>-/-</sup> mice developed normally and showed subtle alterations of immune cell populations in the bone marrow, thymus, spleen, blood and peritoneal cavity that contained notably more anti-inflammatory B-1a cells and less NK cells. In vitro, SIRT2/3 <sup>-/-</sup> macrophages favored fatty acid oxidation (FAO) over glycolysis and produced increased levels of both proinflammatory and anti-inflammatory cytokines. In line with metabolic adaptation and increased numbers of peritoneal B-1a cells, SIRT2/3 <sup>-/-</sup> mice were robustly protected from endotoxemia. Yet, SIRT2/3 double deficiency did not modify endotoxin tolerance. Overall, these data suggest that sirtuins can act in concert or compensate each other for certain immune functions, a parameter to be considered for drug development. Moreover, inhibitors targeting multiple sirtuins developed for clinical purposes may be useful to treat inflammatory diseases.
Keywords
cytokine, endotoxemia, inflammation, innate immunity, macrophage, metabolism, sepsis, sirtuins
Pubmed
Web of science
Open Access
Yes
Create date
19/12/2019 12:17
Last modification date
07/01/2020 7:26
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