Abstract—
TLR4 signal activated by lipopolysaccharide (LPS) is involved in the pathological process of the central nervous system (CNS) diseases and the suppression of TLR4 signal may become an effective treatment. TLR4-IN-C34, a TLR4 inhibitor, is expected to become a candidate compound with anti-neuroinflammatory response. In the present study, the anti-neuroinflammatory effects and possible mechanism of TLR4-IN-C34 were investigated in BV2 microglia cells stimulated by LPS. The results showed that TLR4-IN-C34 decreased the levels of pro-inflammatory factors and chemokines including NO, TNF-α, IL-1β, IL-6, and MCP-1 in the supernatant of LPS-stimulated BV2 cells. Further research indicated that TLR4-IN-C34 suppressed the expression or phosphorylation levels of inflammatory proteins regarding TLR4/MyD88/NF-κB/NLRP3 signaling pathway. In addition, TLR4-IN-C34 reduced ROS production in BV2 cells after LPS treatment. In conclusion, our findings suggest that anti-neuroinflammatory activity of TLR4-IN-C34 may be interrelated to the inhibition of TLR4/MyD88/NF-κB/NLRP3 signaling pathway and reduction of ROS generation.
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Funding
This project was supported by the National Key R&D Program of China (2020YFC2008302), the National Natural Science Foundation of China (81473383), and the Medical and Health Innovation Project of Chinese Academy of Medical Sciences (2016-I2M-3–007).
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Yue-Hua Wang and Guan-Hua Du designed the experiments; Shan-Shan Zhang, Man Liu, Dong-Ni Liu, and Ying-Lin Yang performed the experiments; Shan-Shan Zhang and Yue-Hua Wang analyzed the data; and all the authors read and approved the final manuscript.
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Zhang, SS., Liu, M., Liu, DN. et al. TLR4-IN-C34 Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses via Downregulating TLR4/MyD88/NF-κB/NLRP3 Signaling Pathway and Reducing ROS Generation in BV2 Cells. Inflammation 45, 838–850 (2022). https://doi.org/10.1007/s10753-021-01588-8
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DOI: https://doi.org/10.1007/s10753-021-01588-8