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.
Highlights
Sepsis is a systemic inflammatory response syndrome (SIRS) that develops when the host organism immune response to severe infection by various pathogenic microorganisms in blood or tissue triggers a life-threatening wholebody inflammatory response
high-mobility group box 1 protein (HMGB1) mRNA expression levels were high after LPS stimulation
The expression level of HMGB1 mRNA in the control group was lower than in the other groups, while HMGB1 mRNA was highly expressed at 24 h after LPS stimulation (P,0.05)
Summary
Sepsis is a systemic inflammatory response syndrome (SIRS) that develops when the host organism immune response to severe infection by various pathogenic microorganisms in blood or tissue triggers a life-threatening wholebody inflammatory response. Sepsis has a higher morbidity rate than myocardial infarction and is the major cause of death for patients in intensive care units without heart disease. Sepsis in patients can be detected by identifying the pathogenic microorganism or observing highly suspicious infection foci. Anti-infective therapy and organ function support technology have been improved greatly, the mortality rate of sepsis remains between 30 and 70%. Because of the expense of treatments and large consumption of medical resources, sepsis seriously affects the quality of human life and poses a great threat to human health
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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