论文部分内容阅读
Introduction Glutamate is a well-defined excitatory neurotransmitter in the central nervous system and contributes to neurotoxicity.However, the function and potential toxicity of glutamate in peripheral tissues are not well defined, especially that in the pathogenesis of inflammation and atherosclerosis.Since macrophage plays an important role in inflammation and atherosclerosis mainly by releasing TNF-α, this study aimed to investigate the effect of glutamate on TNF-α release in macrophage.Methods Confocal microscopy plus immunofluorescence were used to estimate the expression of ionotropic glutamate receptors in the RAW264.7 macrophages;ELISA,flow cytometry and Western blotting were used to detect TNF-α release, the production of reactive oxygen species (ROS) and the protein expression level of TNF-α, respectively.Results The results showed that all the three types of ionotropic glutamate receptors (NMDA receptor, AMPA receptor and kinate receptor) were expressed in the RAW264.7 macrophages.Glutamate significantly stimulated the TNF-αt release in RAW264.7 macrophages, and this effect was predominantly mediated by the AMPA receptor, as antagonizing the AMPA receptor significantly decreased the TNF-α release.TNF-α release was accompanied by an elevation of ROS production.Suppressing the activities of ROS or NF-κB decreased the TNF-α production in the RAW264.7 macrophages.NMDA receptor activation induced minor TNF-α release compared with the AMPA receptor.Conclusions Three types of ionotropic glutamate receptors are expressed in the RAW264.7 macrophages.Glutamate stimulates TNF-α release mainly via the AMPA receptor.The release of TNF-α after AMPA receptor activation in RAW264.7 macrophages is likely mediated by ROS/NF-κB signaling.The results suggest that glutamate may participate in inflammation and contribute to atherosclerosis.