Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

Abstract

This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.

Propofol inhibits the release of interleukin-6, 8 and tumor necrosis factor-α correlating with high-mobility group box 1 expression in lipopolysaccharides-stimulated RAW 264.7 cells

“…Studies have shown that it can produce the corresponding cytokines and inflammatory mediators, such as TNF-α, IL-1β and IL-6 and so on as long as the mouse macrophage RAW264.7 cells are stimulated by LPS [ 13 ]. Propofol is widely used in the induction and maintenance of general anesthesia, and recent studies have shown that propofol can down-regulate the expression levels of HMGB1 messenger ribonucleic acid and protein [ 10 ]. Our study found that the expression of HMGB1 in RAW 264.7 cells in LPS intervention group was significantly increased, as compared with the blank control group after RAW 264.7 cells were stimulated by LPS for 16 h. Furthermore, compared with the blank control group, the expressions of HMGB1 in low-dose group of propofol and the high-dose group were also up-regulated.…”

“…The results suggested that LPS stimulation increased the expression of HMGB1. Previous studies have found HMGB1 as an important inflammatory mediator and proinflammatory cytokine, which links in response networks of sepsis proinflammatory cytokine [ 10 , 14 – 17 ]. LPS and various cytokines can stimulate the release of HMGB1, while HMGB1 can stimulates the synthesis of pro-inflammatory cytokines [ 8 ].…”

“…Studies have found that propofol can block endotoxin-induced monocyte-macrophages to produce various inflammatory factors [ 3 , 5 , 9 ]. LPS stimulation can induce HMGB1 release from mouse macrophages, however, propofol can inhibit this process leading to downregulation of HMGB1 mRNA and also block the activation of nuclear transcription factor-κB (NF-κB) [ 10 ]. In addition, the propofol can inhibit the expression of toll-like receptor 4 (TLR-4) and NF-κB to block the activation of p38 mitogen-activated protein kinase and the expression of pro-inflammatory cytokines [ 4 ].…”

Effects of propofol pretreatment on lung morphology and heme oxygenase-1 expression in oleic acid-induced acute lung injury in rats

“…It can regulate innate immunity and the expression of proinflammatory signals in sepsis 10,11 . It can also reduce the expression of toll-like receptor 2/4 in sepsis 12,13 , attenuate the expression of NF-κB in sepsis 14 , and upregulate the expression ofHO-1 15 . Although propofol is known to increase the expression of HO-1 in ALI, its effects on morphological changes in the lungs remain unexplored.…”

Macrophage Inflammatory Protein-2 in High Mobility Group Box 1 Secretion of Macrophage Cells Exposed to Lipopolysaccharide

“…Moreover, NF-κB p65 signalling is also responsible for HMGB1 expression [59]. Under normal conditions, NF-κB p65 is bound to IκB (its endogenous inhibitor) in the cytoplasm, but upon LPS stimulation, IκB dissociates from the NF-κB-IκB complex and is degraded.…”