Sirtuins and Immuno-Metabolism of Sepsis

Autor: Xianfeng Wang, Nancy L. Buechler, Alan G. Woodruff, David L. Long, Manal Zabalawi, Barbara K. Yoza, Charles E. McCall, Vidula Vachharajani
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 19, Iss 9, p 2738 (2018)
Druh dokumentu: article
ISSN: 1422-0067
DOI: 10.3390/ijms19092738
Popis: Sepsis and septic shock are the leading causes of death in non-coronary intensive care units worldwide. During sepsis-associated immune dysfunction, the early/hyper-inflammatory phase transitions to a late/hypo-inflammatory phase as sepsis progresses. The majority of sepsis-related deaths occur during the hypo-inflammatory phase. There are no phase-specific therapies currently available for clinical use in sepsis. Metabolic rewiring directs the transition from hyper-inflammatory to hypo-inflammatory immune responses to protect homeostasis during sepsis inflammation, but the mechanisms underlying this immuno-metabolic network are unclear. Here, we review the roles of NAD+ sensing Sirtuin (SIRT) family members in controlling immunometabolic rewiring during the acute systemic inflammatory response associated with sepsis. We discuss individual contributions among family members SIRT 1, 2, 3, 4 and 6 in regulating the metabolic switch between carbohydrate-fueled hyper-inflammation to lipid-fueled hypo-inflammation. We further highlight the role of SIRT1 and SIRT2 as potential “druggable” targets for promoting immunometabolic homeostasis and increasing sepsis survival.
Databáze: Directory of Open Access Journals
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