Sirtuins and Immuno-Metabolism of Sepsis
Abstract
:1. Introduction
2. Immunologic Dysfunction in Sepsis
3. Metabolic and Bioenergetic Changes during Sepsis
3.1. Microenvironment Contributions
3.2. Metabolic Changes during Hyper-Inflammation
3.3. Metabolic Changes during Hypo-Inflammation
4. Sirtuins and Sepsis Immuno-Metabolism
4.1. SIRT1
4.2. SIRT2
4.3. SIRT3
4.4. SIRT4
4.5. SIRT6
4.6. SIRT5 and SIRT7
5. Sirtuin Modulation as Potential Therapeutic Targets?
5.1. Sirtuin Modulation during Hyper-Inflammation
5.2. Sirtuin Modulation during Hypo-Inflammation
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Sir2 | Silent mating-type information regulator 2 |
SIRT | Sirtuin |
ADP | Adenosine diphosphate |
ATP | Adenosine triphosphate |
NAD | Nicotinamide adenine dinucleotide |
NAMPT | Nicotinamide phosphoribosyltransferase |
GLUT | Glucose transporter |
PDC | Pyruvate dehydrogenase complex |
Acetyl-CoA | Acetyl coenzyme A |
NADPH | Nicotinamide adenine dinucleotide phosphate |
ROS | Reactive oxygen species |
TCA | Tricarboxylic acid |
CPT1 | Carnitine palmitoyltransferase 1 |
STAT6 | Signal transducer and activator of transcription 6 |
PPAR | Peroxisome proliferator-activated receptor |
PGC | Peroxisome proliferator-activated receptor gamma coactivator |
FOXO1 | Forkhead box protein O1 |
HIF | Hypoxia inducible factor |
LD | linear dichroism |
UCP1 | Uncoupling protein 1 |
PDH | Pyruvate dehydrogenase |
ACLY | ATP-citrate lyase |
PEPCK1 | Phosphoenolpyruvate carboxykinase 1 |
OXPHOS | Oxidative phosphorylation |
NFĸB | Nuclear factor kappa B |
TNF | Tumor necrosis factor |
H3K9 | Histone 3; lysine 9 |
CD36 | Cluster of differentiation 36 |
AMPK | AMP-activated protein kinase |
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Sirtuin | Immune Cell Type | Mechanism of Action |
---|---|---|
SIRT1 | Monocytes | Direct NFκB p65 deacetylation and the HIF-1α and PGC-1α pathway [14] |
Macrophages | Phenotypic shift from activator to suppressor cells [19] | |
Lymphocytes | Suppression of pro-inflammatory cytokine expression [71] | |
Endothelial cells | Direct NFκB p65 deacetylation: attenuation of pro-inflammatory adhesion molecule expression [79] | |
SIRT2 | Macrophages | Direct NFκB p65 deacetylation and polarization to suppressor phenotype: STAT6/GATA3 signaling cascade [80]. Direct NFκB p65 deacetylation: attenuation of pro-inflammatory cytokine expression [13] |
SIRT3 | Monocytes | Mitochondrial biogenesis and increased oxidative phosphorylation to sustain hypo-inflammation [9] |
SIRT4 | Monocytes | Resolution of hypo-inflammatory phase; restoration of glucose oxidation via PDC activity and SIRT1 repression [81] |
Endothelial cells | Attenuation of pro-inflammatory cytokine and adhesion molecule expression via blocking of nuclear translocation of NFκB p65 [82] | |
SIRT6 | Monocytes | Decreases glucose oxidation and glycolysis during the hypo-inflammatory phase via epigenetic repression of HIF-1α [7] |
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Wang, X.; Buechler, N.L.; Woodruff, A.G.; Long, D.L.; Zabalawi, M.; Yoza, B.K.; McCall, C.E.; Vachharajani, V. Sirtuins and Immuno-Metabolism of Sepsis. Int. J. Mol. Sci. 2018, 19, 2738. https://doi.org/10.3390/ijms19092738
Wang X, Buechler NL, Woodruff AG, Long DL, Zabalawi M, Yoza BK, McCall CE, Vachharajani V. Sirtuins and Immuno-Metabolism of Sepsis. International Journal of Molecular Sciences. 2018; 19(9):2738. https://doi.org/10.3390/ijms19092738
Chicago/Turabian StyleWang, Xianfeng, Nancy L. Buechler, Alan G. Woodruff, David L. Long, Manal Zabalawi, Barbara K. Yoza, Charles E. McCall, and Vidula Vachharajani. 2018. "Sirtuins and Immuno-Metabolism of Sepsis" International Journal of Molecular Sciences 19, no. 9: 2738. https://doi.org/10.3390/ijms19092738
APA StyleWang, X., Buechler, N. L., Woodruff, A. G., Long, D. L., Zabalawi, M., Yoza, B. K., McCall, C. E., & Vachharajani, V. (2018). Sirtuins and Immuno-Metabolism of Sepsis. International Journal of Molecular Sciences, 19(9), 2738. https://doi.org/10.3390/ijms19092738