Meng Tao, Yu Jingya, Lei Zhen, Wu Jianbo, Wang Shuqin, Bo Qiyu, Zhang Xinyu, Ma Zhiyong, Yu Jingui
Department of Anesthesiology, Qilu Hospital of Shandong University, Shandong University, No. 107 Wen Hua Xi Road, Jinan, Shandong 250012, China.
Department of Pathogeny Biology, Shandong University School of Medicine, No. 44 Wen Hua Xi Road, Jinan, Shandong 250012, China.
Clin Dev Immunol. 2013;2013:325481. doi: 10.1155/2013/325481. Epub 2013 Nov 26.
During an infection, lipopolysaccharide (LPS) stimulates the production of reactive oxygen species (ROS), which is mediated, in large part, by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs); NOX2 is the major NOX isoform found in the macrophage cell membrane. While the immunomodulatory activity of propofol is highly documented, its effect on the LPS-induced NOX2/ROS/NF-κB signaling pathway in macrophages has not been addressed. In present study, we used murine macrophage cell line RAW264.7 pretreated with propofol and stimulated with LPS. IL-6 and TNF-α expression, ROS production, and NOX activity were determined. Results showed that propofol attenuated LPS-induced TNF-α and IL-6 expression. Moreover, LPS-stimulated phosphorylation of NF-κB and generation of ROS were weakened in response to propofol. Propofol also reduced LPS-induced NOX activity and expression of gp91phox and p47phox. We conclude that propofol modulates LPS signaling in macrophages by reducing NOX-mediated production of TNF-α and IL-6.
在感染过程中，脂多糖（LPS）刺激活性氧（ROS）的产生，这在很大程度上由烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOXs）介导；NOX2是巨噬细胞膜中发现的主要NOX亚型。虽然丙泊酚的免疫调节活性有大量文献记载，但其对巨噬细胞中LPS诱导的NOX2/ROS/NF-κB信号通路的影响尚未得到探讨。在本研究中，我们使用经丙泊酚预处理并受LPS刺激的小鼠巨噬细胞系RAW264.7。测定了白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达、ROS的产生以及NOX活性。结果表明，丙泊酚减弱了LPS诱导的TNF-α和IL-6表达。此外，丙泊酚使LPS刺激的NF-κB磷酸化和ROS生成减弱。丙泊酚还降低了LPS诱导的NOX活性以及gp91phox和p47phox的表达。我们得出结论，丙泊酚通过减少NOX介导的TNF-α和IL-6产生来调节巨噬细胞中的LPS信号传导。
