关键词: cytokines extracellular vesicles lipopolysaccharide neuroinflammation proteomics

来  源:   DOI:10.1002/jex2.165   PDF(Pubmed)

Abstract:
Neuroinflammation is initiated through microglial activation and cytokine release which can be induced through lipopolysaccharide treatment (LPS) leading to a transcriptional cascade culminating in the differential expression of target proteins. These differentially expressed proteins can then be packaged into extracellular vesicles (EVs), a form of cellular communication, further propagating the neuroinflammatory response over long distances. Despite this, the EV proteome in the brain, following LPS treatment, has not been investigated. Brain tissue and brain derived EVs (BDEVs) isolated from the cortex of LPS-treated mice underwent thorough characterisation to meet the minimal information for studies of extracellular vesicles guidelines before undergoing mass spectrometry analysis to identify the differentially expressed proteins. Fourteen differentially expressed proteins were identified in the LPS brain tissue samples compared to the controls and 57 were identified in the BDEVs isolated from the LPS treated mice compared to the controls. This included proteins associated with the initiation of the inflammatory response, epigenetic regulation, and metabolism. These results allude to a potential link between small EV cargo and early inflammatory signalling.
摘要:
神经炎症是通过小胶质细胞活化和细胞因子释放引发的,这可以通过脂多糖治疗(LPS)诱导,导致转录级联反应,最终导致靶蛋白的差异表达。然后可以将这些差异表达的蛋白质包装到细胞外囊泡(EV)中,一种形式的蜂窝通信,进一步传播长距离的神经炎症反应。尽管如此,大脑中的EV蛋白质组,LPS治疗后,没有被调查。在进行质谱分析以鉴定差异表达的蛋白质之前,从LPS处理的小鼠的皮质分离的脑组织和脑源性EV(BDEV)进行了彻底的表征,以满足细胞外囊泡指南研究的最少信息。与对照相比,在LPS脑组织样品中鉴定了14种差异表达的蛋白质,与对照相比,在从LPS处理的小鼠分离的BDEV中鉴定了57种。这包括与炎症反应起始相关的蛋白质,表观遗传调控,和新陈代谢。这些结果暗示了小EV货物和早期炎症信号之间的潜在联系。
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