Melatonin Ameliorates Lipopolysaccharide-Induced Microglial Inflammation via Triggering SIRT1/HMGB1 Signaling Axis
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Melatonin Ameliorates Lipopolysaccharide-Induced Microglial Inflammation via Triggering SIRT1/HMGB1 Signaling Axis Enkhmurun Chibaatar 1,3 & Kai Le 2 & Idriss Ali Abdoulaye 1,3 & Shanshan Wu 1,3 & Yijing Guo 1 Received: 9 June 2020 / Accepted: 3 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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, wellknown 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, IL6, 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. Keywords HMGB1 . Melatonin . Microglia . Neuroinflammation
Introduction Stroke is one of the major public health problems with great morbidity and mortality rate. Depending on stroke’s severity and consequences, patients need long-term treatment and care which result in great economic and society burden (Rajsic et al. 2019). Although many molecular and cellular mechanisms have been implicated in the pathophysiological
Enkhmurun Chibaatar and Kai Le are co-first authors * Yijing Guo [email protected] 1
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, Jiangsu Province, China
2
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
3
School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
processes of stroke, it is generally con
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