Abstract
Stroke is one of the highest incidence neurological disorder with great morbidity and mortality rate. The secondary neuroinflammation contributed by microglial activation is a consequential response observed in the pathogenesis of stroke. High-mobility group box 1, a non-histone nuclear protein, interacts with immune cells, such as microglia, and leads to a cascade amplification of the secondary neuroinflammatory responses, which are related to neuronal damage later. Melatonin is a neurohormone, well-known as its anti-oxidative and anti-inflammatory effects. However, until now, more findings are required for better understanding about anti-inflammatory effect of melatonin on HMGB1 and HMGB1-triggered pathway in LPS-induced microglial activation. Melatonin effect on the viability of BV2 microglial cells was measured by CCK-8 assay; mRNA levels of HMGB1 and other inflammatory cytokines were determined by quantitative real-time polymerase chain reaction assay or enzyme-linked immunosorbent assays; the protein expression levels of TLR4/MyD88/NF-κB and SIRT1 were detected by Western blot, and HMGB1 translocation and release from BV2 microglial cells were examined by immunofluorescence assay. The results of this study demonstrated that melatonin suppressed LPS-triggered BV2 microglial activation-mediated inflammation by inhibiting high expression and release of HMGB1 and moderating the activation of subsequent TLR4/MyD88/NF-κB signaling pathway, which was activated by SIRT1 elevation. Furthermore, LPS-induced expression of pro-inflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β) was notably reversed by melatonin pre-treatment. In summary, our findings suggest that melatonin may act as a promising therapeutic agent for reducing post-stroke neuroinflammation by targeting HMGB1 and the subsequent signaling axis.
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The datasets used and/or analyzed in the current study are available from the corresponding author on reasonable request.
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This study was supported by the National Natural Science Foundation of China (no. 81471187).
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All authors contributed to the study conception and design. This study was supervised by Yijing Guo. Material preparation, data collection, and analysis were performed by Enkhmurun Chibaatar, Kai Le, Idriss Ali Abdoulaye, and ShanShan Wu. The first draft of the manuscript was written by Enkhmurun Chibaatar, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Chibaatar, E., Le, K., Abdoulaye, I.A. et al. Melatonin Ameliorates Lipopolysaccharide-Induced Microglial Inflammation via Triggering SIRT1/HMGB1 Signaling Axis. J Mol Neurosci 71, 691–701 (2021). https://doi.org/10.1007/s12031-020-01699-1
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DOI: https://doi.org/10.1007/s12031-020-01699-1