In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation

作者：Jing Jing Li, Bin Wang, Mahesh Chandra Kodali, Chao Chen, Eun‐Hee Kim, Benjamin J. Patters, Lu-Bin Lan, Santosh Kumar, Xinjun Wang, Junming Yue, Francesca‐Fang Liao · 发表于：Journal of Neuroinflammation · 年份：2018 · DOI：10.1186/s12974-017-1038-8 · 被引用次数：201 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Extracellular vesicles in disease、MicroRNA in disease regulation

BACKGROUND: Neuroinflammation is implicated in the development and progression of many neurodegenerative diseases. Conditions that lead to a peripheral immune response are often associated with inflammation in the central nervous system (CNS), suggesting a communication between the peripheral immune system and the neuroimmune system. The underlying mechanism of this relationship remains largely unknown; however, experimental studies have demonstrated that exposure to infectious stimuli, such as lipopolysaccharide (LPS) or high-fat diet (HFD) feeding, result in profound peripheral- and neuro-inflammation. METHODS: Using the model of endotoxemia with LPS, we studied the role of serum-derived exosomes in mediating neuroinflammation. We purified circulating exosomes from the sera of LPS-challenged mice, which were then intravenously injected into normal adult mice. RESULTS: We found that the recipient mice that received serum-derived exosomes from LPS-challenged mice exhibited elevated microglial activation. Moreover, we observed astrogliosis, increased systemic pro-inflammatory cytokine production, and elevated CNS expression of pro-inflammatory cytokine mRNA and the inflammation-associated microRNA (miR-155) in these recipient mice. Gene expression analysis confirmed that many inflammatory microRNAs were significantly upregulated in the purified exosomes under LPS-challenged conditions. We observed accumulated signaling within the microglia of mice that received tail-vein injec...