Regulatory Roles of the PI3K/Akt Signaling Pathway in Rats with Severe Acute Pancreatitis

Abstract

The phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) pathway plays a key role in inflammation. However, the regulatory roles of PI3K/Akt in severe acute pancreatitis (SAP) have not been elucidated. The aim of this study was to investigate the impact of wortmannin, a PI3K/Akt inhibitor, on SAP rats through exposure to sodium taurocholate (STC) after 3 h and 6 h. The SAP group was found to have a significant increase in pancreas Akt expression, along with the activation of serum amylase, TNF-α, IL-1β, and IL-6, and pancreas histological aggravation. The administration of wortmannin in SAP rats reduced Akt expression, attenuated the level of serum amylase and inflammation factor, and alleviated the damage of pancreatic tissue. Furthermore, the administration of wortmannin led to an obvious reduction in NF-κB and p38MAPK expression in SAP rats. These findings showed that the PI3K/Akt inhibitor wortmannin decreases inflammatory cytokines in SAP rats and suggests its regulatory mechanisms may occur through the suppression on NF-κB and p38MAPK activity.

The ACE2-Angiotensin-(1–7)-Mas Axis Protects Against Pancreatic Cell Damage in Cell Culture

“…IL-8 stimulates PI3K/AKT pathway, whereas IL-6 and IL-6R combination mainly exert their effects through activation of the JAK/STAT signal transduction pathway, the Ras/Erk, and PI3K signaling pathways. Xu et al 52 have shown that the PI3K/ AKT inhibitor wortmannin decreased inflammatory cytokines in SAP. The PI3K/AKT inhibitor may regulate PI3K/AKT signaling mediated by a reduction in the activation of nuclear factor-κB and p38MAPK activity and the down-regulation of transcription of NF-κB-dependent proinflammatory genes, including TNF-α, IL-1β, and IL-6 in SAP rats.…”

A multi-targeted approach to suppress tumor-promoting inflammation

“…In vivo tests on rodents (rat paw edema) also suggest that AKT inhibitors prevent AKT phosphorylation and downregulate the expression of inflammatory factors IL-6, MCP-1,TNFα and iNOS [239]. Similarly, in research on pancreatitis, researchers have found that AKT inhibition mediates a reduction in the activation of NF-κB and p38MAPK activity in SAP rats and a downregulation of NF-κB-dependent proinflammatory genes, including TNF-α, IL-1β and IL-6 [240]. …”

Lipoic Acid in the Prevention of Acute Kidney Injury

“…In a rat model of myocardial IRI, pretreatment of erythropoietin led to significant decrease in the levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α). The effects of EPO were found to be associated with the activation of PI3K/Akt signaling, which suppressed the inflammatory responses [42]. Similarly, in a rat model with severe acute pancreatitis, Akt expression in pancreas was significantly increased, along with the activation of cytokines (TNF-α, IL-1β, and IL-6, IL-1β and TNF-α).…”