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Propofol Attenuates Airway Inflammation in a Mast Cell-Dependent Mouse Model of Allergic Asthma by Inhibiting the Toll-like Receptor 4/Reactive Oxygen Species/Nuclear Factor κB Signaling Pathway

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Abstract

Propofol, an intravenous anesthetic agent widely used in clinical practice, is the preferred anesthetic for asthmatic patients. This study was designed to determine the protective effect and underlying mechanisms of propofol on airway inflammation in a mast cell-dependent mouse model of allergic asthma. Mice were sensitized by ovalbumin (OVA) without alum and challenged with OVA three times. Propofol was given intraperitoneally 0.5 h prior to OVA challenge. The inflammatory cell count and production of cytokines in the bronchoalveolar lavage fluid (BALF) were detected. The changes of lung histology and key molecules of the toll-like receptor 4 (TLR4)/reactive oxygen species (ROS)/NF-κB signaling pathway were also measured. The results showed that propofol significantly decreased the number of eosinophils and the levels of IL-4, IL-5, IL-6, IL-13, and TNF-α in BALF. Furthermore, propofol significantly attenuated airway inflammation, as characterized by fewer infiltrating inflammatory cells and decreased mucus production and goblet cell hyperplasia. Meanwhile, the expression of TLR4, and its downstream signaling adaptor molecules—–myeloid differentiation factor 88 (MyD88) and NF-κB, were inhibited by propofol. The hydrogen peroxide and methane dicarboxylic aldehyde levels were decreased by propofol, and the superoxide dismutase activity was increased in propofol treatment group. These findings indicate that propofol may attenuate airway inflammation by inhibiting the TLR4/MyD88/ROS/NF-κB signaling pathway in a mast cell-dependent mouse model of allergic asthma.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 81250026), Graduate Student Innovation Foundation of Peking Union Medical College (201510020202), and Initial Scientific Research foundation for talent introduction of China–Japan Friendship Hospital.

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Authors and Affiliations

  1. Department of Anesthesiology, Peking Union Medical College Hospital, No. 1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China

    Hong-Yi Li, Jing-Xia Meng, Zhen Liu, Xiao-Wen Liu & Yu-Guang Huang

  2. Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33# Shijingshan District, Beijing, 100144, China

    Xiao-Wen Liu

  3. Department of Anesthesiology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing, 100029, China

    Jing Zhao

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  1. Hong-Yi Li
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Li, HY., Meng, JX., Liu, Z. et al. Propofol Attenuates Airway Inflammation in a Mast Cell-Dependent Mouse Model of Allergic Asthma by Inhibiting the Toll-like Receptor 4/Reactive Oxygen Species/Nuclear Factor κB Signaling Pathway. Inflammation 41, 914–923 (2018). https://doi.org/10.1007/s10753-018-0746-2

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