• Cheng-Hua Zhou, Yang-Zi Zhu, Pan-Pan Zhao, Chun-Mei Xu, Ming-Xing Zhang, He Huang, Jing Li, Lu Liu, and Yu-Qing Wu.
• From the *Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, PR China; †Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, PR China; and ‡Department of Anesthetic Pharmacology, Xuzhou Medical College, Xuzhou, PR China.
• Anesth. Analg.. 2015 Jun 1;120(6):1361-8.

BackgroundIn this study, we investigated the effect of propofol, a commonly used IV anesthetic, on lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes and explored the molecular mechanisms by which it occurs.MethodsAstrocytes were stimulated with LPS (1.0 μg/mL) in the absence and presence of different concentrations of propofol. The expression of astrocyte marker glial fibrillary acidic protein (GFAP) in astrocytes was detected using immunofluorescence staining and Western blot analysis. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α were measured using an enzyme-linked immunosorbent assay. The mRNA level of Toll-like receptor 4 (TLR4) was determined by semiquantitative reverse transcriptase-polymerase chain reaction. The protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), p- extracellular signal-regulated protein kinases (ERK)1/2, p-c-Jun N-terminal kinase, p-p38 mitogen-activated protein kinase (MAPK), p-I-κBα, I-κBα, and p-nuclear factor-κB (NF-κB)p65 were detected by Western blot.ResultsOur results show that after stimulation with LPS, the levels of IL-1β, IL-6, and tumor necrosis factor-α and the expression of GFAP in astrocytes were up-regulated significantly. In addition, the expression of TLR4, MyD88, p-ERK1/2, p-c-Jun N-terminal kinase, p-p38 MAPK, and p-NF-κBp65 increased, whereas the expression of total I-κBα decreased upon stimulation with LPS. Propofol (10 μM) reduced the secretion of proinflammatory cytokines, inhibited the expressions of GFAP, TLR4, MyD88, p-ERK1/2, p-p38 MAPK, and p-NF-κBp65 in astrocytes challenged with LPS.ConclusionsIn the present study, propofol 10 μM but not lower clinically relevant or higher supra-clinical concentrations attenuated LPS-induced astrocyte activation and subsequent inflammatory responses by inhibiting the TLR4/MyD88-dependent NF-κB, ERK1/2, and p38 MAPK pathways.

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