Critical Care Research and Practice

Review Article

Emerging Evidence concerning the Role of Sirtuins in Sepsis

Table 1

Relationship between SIRT1 activation and sepsis-induced cell damage.


Sepsis model	Main treatment	Effects	Reference

LPS-induced macrophages or septic-shock mice	SIRT1 activation	IL-6 and TNF-α secretion is inhibited.	[21]
High glucose and LPS-induced RAW264.7 cells	SIRT1 activation	IL-1β and TNF-α secretion is reduced.	[22]
Septic obese mice and LPS-simulated HUVECs	SIRT1 activation	Leukocyte/platelet adhesion and E-selectin/ICAM-1 expression levels are decreased, and animal survival is improved.	[23]
LPS-induced THP1 cells	SIRT1 activation by resveratrol	Repressed transcription of TNF-α.	[24]
Septic mice	SIRT1 activation	NF-κB is deacetylated, redox balance and mitochondrial homeostasis are restored, and NLRP3 inflammasomes are inhibited.	[25]
RAW264.7 cells	SIRT1 activation by calorie restriction	NF-κB in its p65 lysine site is deacetylated.	[26]
Septic mice	SIRT1 activation	HMGB1 protein expression is reduced.	[27]
Hepatocytes from CLP mouse model/LPS-stimulated L02 cells	SIRT1 activation	HMGB1 translocation is inhibited.	[28]
THP-1 cells, murine bone marrow-derived macrophages, and CLP mice	SIRT1 activation by poly (ADP-ribose) polymerase	Increased HMGB1 nuclear retention and decreased extracellular secretion.	[29]
RAW264.7 cells and CLP mice	SIRT1 activation	Directly interacts with HMGB1 via its N-terminal lysine residues [24, 29, 30]. Inhibits HMGB1 release and improves animal survival.	[30]
Renal epithelial cells in CLP rats	SIRT1 activation by resveratrol or SRT1720	Deacetylates SOD2, reduces oxidative stress, promotes mitochondrial function, and improves animal survival.	[31]
CLP mice and septic encephalopathy	SIRT1 activation by melatonin	Deacetylates p53, FOXO1, and NF-κB. Improves the survival rate, attenuates brain edema and neuronal apoptosis, and preserves BBB integrity.	[32]
Human monocyte cell model of endotoxin tolerance and human leukocytes from sepsis	SIRT1 activation	Deacetylated RelA/p65 lysine 310 and nucleosomal histone H4 lysine 16 to promote termination of NF-κB dependent transcription.	[33]