Department of Anesthesiology and Pain Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
Department of Anesthesiology and Pain Medicine, Juntendo Tokyo Koto Geriatric Medical Center, 3-3-20 Shinsuna, Koto-Ku, Tokyo 136-0075, Japan.
Int J Mol Sci. 2022 Sep 3;23(17):10096. doi: 10.3390/ijms231710096.
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.
神经炎症,即炎症细胞因子过度产生,会导致谵妄的发病机制。小胶质细胞通过在感染、组织损伤和神经退行性变时产生和释放炎症细胞因子,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 通过对小胶质细胞发挥抗炎作用来缓解谵妄。在本研究中,我们研究了 DEX 对人小胶质细胞 HMC3 细胞的抗炎作用。结果表明,DEX 部分抑制了脂多糖(LPS)刺激的 HMC3 细胞中 IL-6 和 IL-8 的产生,以及 p38 MAPK 和 IκB 的磷酸化和 NF-κB 的易位。此外,DEX 还可显著抑制未刺激的 HMC3 细胞中 IL-6 和 IL-8 的产生,以及 p38 MAPK 和 IκB 的磷酸化和 NF-κB 的易位。这些观察结果表明,DEX 不仅对 LPS 刺激的小胶质细胞,而且对未刺激的小胶质细胞均具有抗炎作用,其机制可能与抑制炎症信号转导和细胞因子产生有关。