Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340

• Main Authors: Bao Y, Zhu Y, He G, Ni H, Liu C, Ma L, Zhang L, Shi D
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-10-01
• Series: Drug Design, Development and Therapy
• Subjects: NF-κB; dexmedetomidine; BV2 microglia cells; postoperative cognitive dysfunction
• Online Access: https://www.dovepress.com/dexmedetomidine-attenuates-neuroinflammation-in-lps-stimulated-bv2-mic-peer-reviewed-article-DDDT

Yang Bao,1,* Yijun Zhu,1,* Guangbao He,1 Hongwei Ni,1 Chenxia Liu,1 Limin Ma,1 Lifeng Zhang,2 Dongping Shi1 1Department of Anesthesiology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai 201800, People’s Republic of China; 2Department of Anesthesiology, Jiading Maternal and Child Health Hospital, Shanghai 201821, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongping ShiDepartment of Anesthesiology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No.1 Chengbei Road, Jiading District, Shanghai, Shanghai 201800, People’s Republic of ChinaEmail [e-mail] Lifeng ZhangDepartment of Anesthesiology, Jiading Maternal and Child Health Hospital, No 1216 Gaotai Road, Jiading District, Shanghai, Shanghai 201821, People’s Republic of ChinaEmail [e-mail]: Dexmedetomidine (Dex) was reported to exhibit anti-inflammatory effect in the nervous system. However, the mechanism by which Dex exhibits anti-inflammation effects on LPS-stimulated BV2 microglia cells remains unclear. Thus, this study aimed to investigate the role of Dex in LPS-stimulated BV2 cells.Methods: The BV2 cells were stimulated by lipopolysaccharides (LPS). BV2 cells were infected with short-hairpin RNAs targeting NF-κB (NF-κB-shRNAs) and NF-κB overexpression lentivirus, respectively. In addition, miR-340 mimics or miR-340 inhibitor was transfected into BV2 cells, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of miR-340 and NF-κB in BV2 cells. CCK-8 was used to detect the viability of BV2 cells. In addition, Western blotting was used to detect the level of NF-κB in LPS-stimulated BV2 cells. The levels of TNF-α, IL-6, IL-1β, IL-2, IL-12, IL-10 and MCP-1 in LPS-stimulated BV2 cells were measured with ELISA.Results: The level of miR-340 was significantly upregulated in Dex-treated BV2 cells. Meanwhile, the level of NF-κB was significantly increased in BV2 cells following infection with lenti-NF-κB, which was markedly reversed by Dex. LPS markedly increased the expression of NF-κB and proinflammatory cytokines in BV2 cells, which were reversed in the presence of Dex. Moreover, miR-340 mimics enhanced the anti-inflammatory effects of Dex in LPS-stimulated BV2 cells via inhibiting NF-κB and proinflammatory cytokines. Furthermore, Dex obviously inhibited LPS-induced phagocytosis in BV2 cells.Conclusion: Taken together, our results suggested that Dex might exert anti-inflammatory effects in LPS-stimulated BV2 cells via upregulation of miR-340. Therefore, Dex might serve as a potential agent for the treatment of neuroinflammation.Keywords: NF-κB, dexmedetomidine, BV2 microglia cells, postoperative cognitive dysfunction