BACKGROUND Sepsis-induced acute kidney injury (AKI) is threatening the patients with sepsis, and nucleotide-binding oligomerization domain-like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is considered to play a critical role in this complication of sepsis and might be regulated by sirtuin1 (SIRT1).
In summary, these results indicated that miR-181a-5p was involved in sepsis through regulating the inflammatory response by targeting SIRT1, suggesting that miR-181a-5p may be a potential target for the treatment of sepsis.
We explored the effect and mechanism of SIRT1 on HMGB1 using a mouse model of cecal ligation and puncture-induced sepsis and LPS-treated human kidney (HK-2) cell line.
This article focuses on the role of SIRT1 in inflammation, especially its targets and involved signaling pathways in sepsis, and tries to provide more convincing evidence for the clinical treatment of sepsis and other inflammatory diseases.
An in vitro model of inflammation in isolated H9c2 cardiomyocytes was used to confirm SIRT1 response to stimulation with lipopolysaccharide (LPS), followed by a murine model of cecal ligation and puncture (CLP) to investigate the molecular and echocardiographic response to sepsis.
Furthermore, inhibition of SIRT1 by EX527 significantly diminished the protective effects of melatonin on sepsis induced liver injury, hyperglycaemia and STAT3 inactivation.
In addition, melatonin significantly increased SIRT1 protein expression in the myocardium of mice with sepsis, while inhibition of SIRT1 by EX527 abolished melatonin's cardioprotection during sepsis.
These results demonstrated that MCPIP1 could alleviate inflammation responses and sepsis associated liver injury by promoting the expression of SIRT1, and miR-9 was involved in the MCPIP1-mediated regulation of SIRT1.
The results suggested that sepsis resulted in cognitive impairment, which was accompanied by the decreased the expression of PSD95 and Synapsin1, increased amount of TUNEL-positive cells and the activation of glias, increased production of TNF-α and IL-1β, increased expression of nuclear p65, Ac- NF-κB, and decreased expression of SIRT1 and cytoplasmic p65.
We further highlight the role of SIRT1 and SIRT2 as potential "druggable" targets for promoting immunometabolic homeostasis and increasing sepsis survival.
These findings support the unifying concept that nuclear NAD<sup>+</sup> sensor SIRT1 broadly coordinates innate and adaptive immune reprogramming during sepsis and is a druggable immunometabolic enhancement target.
Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317.
Here, we show that nuclear SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogenesis, which alters bioenergetics during sepsis adaptation.
Modifying SIRT-1 activity, which can prevent or treat established sepsis in mice, may provide a new way to treat sepsis by epigenetically restoring immunometabolic homeostasis.
To support the coordination of bioenergetics in human sepsis, we observed elevated NAD(+) levels concomitant with SIRT1 and RelB accumulation at the TNF-α promoter of endotoxin tolerant sepsis blood leukocytes.