Overexpression of NLRC3 enhanced inhibition effect of sevoflurane on inflammation in an ischaemia reperfusion cell model

Abstract

Brain ischaemia is one of the leading causes of mortality and disability worldwide, and the damage caused by ischaemia not only induces primary damage but also that induced by ischaemia-reperfusion (I/R) injury. Multiple processes including inflammation and oxidative stress response play important roles in the development of brain ischaemia injury. Sevoflurane is a well-known volatile anaesthetic, and a recent study discovered the role of sevoflurane in suppression of the inflammation response process via inhibition of inflammatory infiltrates and production, maintaining the balance of cytokine responses, although the possible mechanism was not fully clear. NLRC3 is a member of the nucleotide-binding domain and leucine-rich repeat containing (NLR) family, and it has been regarded as a regulator of the inflammation process via the regulation of inflammasome formation, which is an initiator of inflammatory events. In the present study, we found that overexpression of NLRC3 reduced the apoptosis in a cellular model of ischaemia reperfusion, and the expression of pro-inflammatory cytokines was also decreased. Further study found that these effects might be mediated by the TRAF6/TLR4/NF-κB signalling pathway. Thus, we speculate that overexpression might enhance the effect of sevoflurane in inhibiting the inflammatory response process in an ischaemia reperfusion model, which might be a new therapeutic strategy.

Incidence of Postoperative Cognitive Dysfunction Following Inhalational vs Total Intravenous General Anesthesia: A Systematic Review and Meta-Analysis

“…27 It is true that the possible role of the anesthetics in the inflammatory cascade is still yet to be clarified, with some evidence favoring the use of inhalational agents, such as sevoflurane, specifically in ischemiareperfusion cell models. 28 However, data favouring inhalational anesthetics in ischemia-reperfusion models were produced in the scenario of cardiopulmonary bypass surgeries, in which the etiopathogenesis of POCD is far more complex and diverse. 29 The population enrolled in our review has a high median age, consequentially to the fact that most of the research on POCD involves elder individuals.…”

Inhalation Versus Total Intravenous Anesthesia: A Literature Review

“…2018). However, the possible role of anesthetics in the inflammatory cascade remains unclear, with some evidence favoring the use of inhalational agents such as sevoflurane specifically in cellular models of ischemia-reperfusion (LI et al 2020).…”

Negative regulator NLRC3: Its potential role and regulatory mechanism in immune response and immune-related diseases

“…The interaction between NLRC3 and the p85 submit of PI3K not only has effect on the PI3K/AKT/mTOR signal axis, but also on PI3K/AKT/FoxO3a or FoxO1 signaling pathways ( 26 ). FoxO3a and FoxO1 contribute to regulate cell proliferation, apoptosis, metabolism, and survival ( 28 ). AKT activates and prevents ubiquitin-mediated degradation of FoxO3a and FoxO1 ( 29 ).…”

“…A large amount of pro-inflammation factors result in neuronal cell death ( 68 ). Sevoflurane was observed to play beneficial roles on cerebral ischemia-reperfusion injury, and NLRC3 enhanced the beneficial effects of sevoflurane on ischemia-reperfusion models ( 28 ). Experimental evidence suggests that the beneficial effects of NLRC3 profited from the anti-inflammatory action via preventing NF-κB signal pathway ( 28 ).…”