Anti-Inflammatory Action of Dexmedetomidine on Human Microglial Cells.

Anti-Inflammatory Action of Dexmedetomidine on Human Microglial Cells.
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DOI:
10.3390/ijms231710096
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发表时间:
2022-09-03
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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神经炎症,其中炎性细胞因子过量产生,有助于谵妄的发病机制。小胶质细胞通过响应感染、组织损伤和神经变性而产生和释放炎性细胞因子在神经炎症中发挥核心作用。右美托咪定(DEX)是一种镇静剂,可降低谵妄的发生率。因此,我们假设DEX可能通过对小胶质细胞的抗炎作用来减轻谵妄。在本研究中,我们研究了DEX对人小胶质细胞HMC 3细胞的抗炎作用。结果表明,DEX可部分抑制脂多糖(LPS)刺激的HMC 3细胞产生IL-6和IL-8,抑制p38 MAPK和IκB的磷酸化及NF-κB的转位。此外,DEX显著抑制未经刺激的HMC 3细胞产生IL-6和IL-8,威尔斯p38 MAPK和IκB的磷酸化和NF-κB的易位。这些观察结果表明,DEX通过抑制炎症信号传导和细胞因子产生,不仅对脂多糖刺激的小胶质细胞,而且对未刺激的小胶质细胞都表现出抗炎作用。
Neuroinflammation, where inflammatory cytokines are produced in excess, contributes to the pathogenesis of delirium. Microglial cells play a central role in neuroinflammation by producing and releasing inflammatory cytokines in response to infection, tissue damage and neurodegeneration. Dexmedetomidine (DEX) is a sedative, which reduces the incidence of delirium. Thus, we hypothesized that DEX may alleviate delirium by exhibiting anti-inflammatory action on microglia. In the present study, we investigated the anti-inflammatory action of DEX on human microglial HMC3 cells. The results indicated that DEX partially suppressed the IL-6 and IL-8 production by lipopolysaccharide (LPS)-stimulated HMC3 cells as well as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. Furthermore, DEX substantially suppressed IL-6 and IL-8 production by unstimulated HMC3 cells as wells as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. These observations suggest that DEX exhibits anti-inflammatory action on not only LPS-stimulated but also unstimulated microglial cells via the suppression of inflammatory signaling and cytokine production.
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