Abstract
ObjectiveThe levels of Foxo3a in the peripheral blood mononuclears cells (PBMCs) before and after treatment were detected in acute obstructive suppurative cholangitis (AOSC) patients to evaluate the associations between Foxo3a and stress hyperglycemia (SHG).MethodsPBMCs were obtained from AOSC patients (n=28) on admission (AP), from patients at 1 week after cure (RP) and from healthy volunteers (HV) (n=14) to evaluate the relationship between the protein levels of Foxo3a and the serum levels of glucose. Signaling pathways, which link inflammation and glycometabolism, simultaneously affecting the expression of Foxo3a, were detected. In addition, cytokines were detected in PBMCs and AOSC mouse models, which were pre-treated with Foxo3a agonist.ResultsThe levels of glucose and p-Foxo3a in the AP were significantly higher than those in the RP and HV, where as the levels of Foxo3a in the AP were lower than those in the RP and HV. Foxo3a levels in the AP normalized against RP were strongly negatively correlated with the glucose levels in the AP normalized against RP. The levels of sphingosine-1-phosphate receptor 2 (S1PR2) in the AP were higher than those in the RP and HV. In addition, inhibition of Foxo3a phosphorylation, coupled with the down-regulation of S1PR2, attenuated the LPS-induced inflammatory response in the PBMCs and AOSC mouse models.ConclusionsFoxo3a is correlated with the dysregulation of glucose homeostasis in the pathogenesis of AOSC-induced sepsis by inhibiting the activation of PI3K/Akt-S1PR2 and NF-κB pathways, hinting at a switched role and therapeutic potentialities in the early stage of sepsis.
Highlights
Acute obstructive suppurative cholangitis (AOSC) is one of the most important and direct causes of deaths in patients with biliary tract diseases [1,2]
Forkhead box O3a (Foxo3a) is correlated with the dysregulation of glucose homeostasis in the pathogenesis of acute obstructive suppurative cholangitis (AOSC)-induced sepsis by inhibiting the activation of phosphatidyl iositol 3-kinase (PI3K)/AktS1PR2 and nuclear factor κB (NF-κB) pathways, hinting at a switched role and therapeutic potentialities in the early stage of sepsis
Mechanical obstructions, such as biliary calculi, biliary ascariasis, and biliary tract tumor, block up the common bile duct, leading to suppurative infection and empyema; high biliary pressure leads to a large number of bacteria and lipopolysaccharide (LPS) translocation into the peripheral blood, further resulting in sepsis, which can cause a series of serious complications, such as septic shock and multiple organ failure [3,4]
Summary
Acute obstructive suppurative cholangitis (AOSC) is one of the most important and direct causes of deaths in patients with biliary tract diseases [1,2]. Mechanical obstructions, such as biliary calculi, biliary ascariasis, and biliary tract tumor, block up the common bile duct, leading to suppurative infection and empyema; high biliary pressure leads to a large number of bacteria and lipopolysaccharide (LPS) translocation into the peripheral blood, further resulting in sepsis, which can cause a series of serious complications, such as septic shock and multiple organ failure [3,4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
