Propofol Pretreatment Prevents Oxygen-Glucose Deprivation/Reoxygenation (OGD/R)-induced Inflammation Through Nuclear Transcription Factor κB (NF-κB) Pathway in Neuroblastoma Cells

Abstract

Background: Inflammation is one of the causes of neuroblastoma progression. Propofol attenuates inflammation by repressing nuclear transcription factor κB (NF-κB) in different diseases. But its effect on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced inflammation is not known. Objective: This study investigated the role and mechanism of action of propofol on OGD/Rinduced inflammation in mouse N2A neuroblastoma cells. Methods: MTT was performed on mouse neuroblastoma cells N2A to assess and select the maximum safe dose of propofol. Next, N2A cells were pretreated with propofol and then, exposed to the OGD condition for 3 h and reoxygenated for 6 h. The content of the inflammatory factors, interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), in the medium was measured by ELISA, while their protein expression was detected by western blot and immunofluorescence. The protein expression of P65, p-P65, IKBα and p-IKBα belonging to the NF-κB pathway was also determined by western blot in N2A cells. To further confirm the mechanism of propofol on OGD/R-induced inflammation in mouse N2A cells, P65 was over-expressed and the above experiments were repeated. Results: Propofol did not affect cell viability of N2A cells even at the maximum concentration used (30 µM), thus, 30 µM of propofol was selected to perform our experiments. Besides, OGD/R induced inflammation and activation of NF-κB pathway with increased p-P65 and p-IKBα expression, and propofol pretreatment inhibited OGD/R induced inflammation and activation of NF-κB pathway in N2A cells. Over-expression of P56 abolished the effects of propofol on OGD/Rinduced inflammation and activation of NF-κB pathway in N2A cells. Conclusion: Our work demonstrated for the first time that propofol pretreatment ameliorated OGD/R induced inflammation via NF-κB pathway modulation in mouse neuroblastoma N2A cells, indicating that propofol might be considered as a potential therapeutic approach to reduce inflammation in neuroblastoma.

Calpain‐2 plays a pivotal role in the inhibitory effects of propofol against TNF‐α‐induced autophagy in mouse hippocampal neurons

“…21 In vitro studies identified propofol could inhibit inflammation in neuroblastoma cells and BV2 microglia. 22,23 We previously reported that propofol may protect against TNF-α-induced hippocampal neuron apoptosis 9 and could attenuate TNF-α-modulated expression of MMP-9 and occludin in cerebral microvascular endothelial cells, thus maintaining BBB permeability. 11,12 Propofol also inhibited neuron autophagy, 24 and further investigation revealed the involvement of calcium and calpains.…”

“…Animal studies carried out in rats indicated that propofol may reduce inflammation‐induced brain injury, 19 by inhibiting excessive activation of microglia 20 and by suppressing inflammasome activation as well as pro‐inflammatory cytokines maturation 21 . In vitro studies identified propofol could inhibit inflammation in neuroblastoma cells and BV2 microglia 22,23 . We previously reported that propofol may protect against TNF‐α‐induced hippocampal neuron apoptosis 9 and could attenuate TNF‐α‐modulated expression of MMP‐9 and occludin in cerebral microvascular endothelial cells, thus maintaining BBB permeability 11,12 .…”

Effects of different depth of anesthesia on perioperative inflammatory reaction and hospital outcomes in elderly patients undergoing laparoscopic radical gastrectomy

“…The possible reasons are as follows: First, Quan and other [ 4 ] studies have shown that the average arterial pressure, heart rate, and blood catecholamine concentration of patients during light anesthesia are higher than those during deep anesthesia. Therefore, compared with deep anesthesia, the body’s stress response is greater during light anesthesia under the same stimulation, which leads to a stronger inflammatory response; second, the results of this study show that the amount of propofol during operation in group L was significantly greater than Group H. Studies have shown that propofol can inhibit the inflammatory response [ 16 ] through the NF-κB pathway. At 72 h after operation (T4), the plasma TNF-α concentration in group H was significantly increased, and at this time, the plasma IL-10 concentration in group H was also significantly higher than that in group L. This may be related to postoperative pain.…”

Activation of Delta-Opioid Receptor Protects ARPE19 Cells against Oxygen-Glucose Deprivation/Reoxygenation-Induced Necroptosis and Apoptosis by Inhibiting the Release of TNF-α

“…It has also been reported that cells release more inflammatory factors with the prolongation of reperfusion. [ 31 , 32 ]. We then determined the time course of changes in TNF- α after reoxygenation, and our results verified this point of view.…”