Effect of docosahexenoic acid on sevoflurane-induced activation of microglia Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and the release of inflammatory mediators

Abstract

Objective To observe the effects of docosahexenoic acid (DHA) on sevoflurane-induced Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB) pathway activation and the release of inflammatory mediators. Metheds N9 cells were assigned to a CON group, a Sevo group and a DHA+Sevo group. After 24 h treatment, cell survival was assessed by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay. Western blot was used to detect the levels of microglial TLR4, MyD88 and inhibitor of NF-κB-α(IκB-α), while the contents of inflammatory mediator tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 in each group were detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the CON group, the survival rate of N9 cells in the Sevo group decreased significantly, while the level of TLR4 and MyD88 protein was increased significantly, the level of IκB-α was significantly decreased, the release of TNF-α and IL-1β and IL-6 was increased significantly (P<0.05). The amounts of IL-1β and IL-10 were increased significantly in the DHA+Sevo group (P<0.05). Compared with the Sevo group, the survival rate in the DHA+Sevo group increased significantly, the level of TLR4 and MyD88 protein decreased significantly, the level of IκB-α was increased significantly, TNF-α, IL-1β and IL-6 release was increased significantly, while IL-10 release was increased significantly(P<0.05). Conclusions DHA inhibits sevoflurane-induced cell damage and activation of TLR4/MyD88/NF-κB signaling pathway, and reduces the release of pro-inflammatory mediators TNF-α, IL-1β and IL-6, and increases anti-inflammatory mediator IL-10 release. Key words: Docosahexenoic acid; Sevoflurane; Microglia; Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway; Inflammatory mediator