Propofol Attenuates Hypoxia-Induced Inflammation in BV2 Microglia by Inhibiting Oxidative Stress and NF-κB/Hif-1α Signaling

Abstract

Hypoxia-induced neuroinflammation typically causes neurological damage and can occur during stroke, neonatal hypoxic-ischemic encephalopathy, and other diseases. Propofol is widely used as an intravenous anesthetic. Studies have shown that propofol has antineuroinflammatory effect. However, the underlying mechanism remains to be fully elucidated. Thus, we aimed to investigate the beneficial effects of propofol against hypoxia-induced neuroinflammation and elucidated its potential cellular and biochemical mechanisms of action. In this study, we chose cobalt chloride (CoCl2) to establish a hypoxic model. We found that propofol decreased hypoxia-induced proinflammatory cytokines (TNFα, IL-1β, and IL-6) in BV2 microglia, significantly suppressed the excessive production of reactive oxygen species, and increased the total antioxidant capacity and superoxide dismutase activity. Furthermore, propofol attenuated the hypoxia-induced decrease in mitochondrial membrane potential andy 2 strongly inhibited protein expression of nuclear factor-kappa B (NF-κB) subunit p65 and hypoxia inducible factor-1α (Hif-1α) in hypoxic BV2 cells. To investigate the role of NF-κB p65, specific small interfering RNA (siRNA) against NF-κB p65 were transfected into BV2 cells, followed by exposure to hypoxia for 24 h. Hypoxia-induced Hif-1α production was downregulated after NF-κB p65 silencing. Further, propofol suppressed Hif-1α expression by inhibiting the upregulation of NF-κB p65 after exposure to hypoxia in BV2 microglia. In summary, propofol attenuates hypoxia-induced neuroinflammation, at least in part by inhibiting oxidative stress and NF-κB/Hif-1α signaling.

Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation

“…Although propofol is typically used as an anesthetic agent, it also functions to eliminate inflammation. Propofol reduces both the gene and cytokine productions of TNF- α in not only CoCl 2 -treated hypoxic BV2 microglia but also cecal ligation and puncture-administrated rat liver [ 16 , 17 ]. In this study, RAW 264.7 cells were pretreated with or without propofol (10 or 25 μ g/ml) followed by infected with DENV for 24 h. ELISA analysis showed that DENV infection significantly increased mouse TNF- α production; however, propofol treatment reduced the cytokine levels in a dose-dependent manner ( Figure 5(a) ).…”

“…In addition to the modulation of cellular inflammation through suppressing COX activity in macrophages, propofol attenuates neuroinflammation. Peng et al found that propofol treatment blocks NF- κ B/Hif-1 α signaling and reduces the gene expressions and cytokine secretions of TNF- α , IL-1 β , and IL-6 in hypoxic BV2 microglia [ 16 ]. Propofol treatment also could remarkably inhibit gene expressions of TNF- α , TLR-4, CD14, and GM-CSF in cultured hepatocytes under LPS stimulation [ 29 ].…”

Propofol alleviates inflammation and apoptosis in HCY‑induced HUVECs by inhibiting endoplasmic reticulum stress

“…Propofol is widely used as an anesthetic and it has been reported to possess anti-inflammatory properties ( 27 ). A previous study identified its role in alleviating inflammation via the inhibition of the NF-κB signaling pathway in allergic asthmatic mice; however, whether it could play a central role in suppressing the NF-κB signaling pathway to reduce inflammation and cell apoptosis remains unclear ( 28 ). In the present study, pretreatment with propofol increased cell viability, reduced apoptosis and ameliorated inflammation by inactivating the NF-κB signaling pathway.…”

Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis

“…Intense studies have revealed that propofol can regulate a plethora of genes related to the activation of microglia [19,[32][33][34]. Previously, we reported that propofol attenuates hypoxia-induced neuroinflammation, at least in part by inhibiting oxidative stress and NF-κB/hypoxia inducible factor-1α (Hif-1α) signaling in BV2 microglia [35]. However, the knowledge of the roles of miRNAs on propofol-induced inactivation of microglia is limited [18].…”

“…miR-221/222 expression can be downregulated by propofol in a dosedependent manner. Interestingly, propofol is sufficient to inhibit several inflammatory signaling pathways, such as NF-κB, p38 MAPK, and JAK1/STAT3 pathway [35][36][37]. Thus, it will be interesting to investigate whether the inactivation of these inflammatory signaling pathways by propofol is responsible for the decrease in the expression of miR-221/222 in microglia.…”