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

Jing Jing Li, Bin Wang, Mahesh Chandra Kodali, Chao Chen, Eunhee Kim, Benjamin John Patters, Lubin Lan, Santosh Kumar, Xinjun Wang, Junming Yue, Francesca-Fang Liao

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 injections of fluorescently labeled exosomes though the percentage of those microglial cells was found low. Finally, purified LPS-stimulated exosomes from blood when infused directly into the cerebral ventricles provoked significant microgliosis and, to a lesser extent, astrogliosis. Conclusions: The experimental results suggest that circulating exosomes may act as a neuroinflammatory mediator in systemic inflammation.

Original languageEnglish (US)
Article number8
JournalJournal of Neuroinflammation
Volume15
Issue number1
DOIs
StatePublished - Jan 8 2018

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Exosomes
Lipopolysaccharides
Inflammation
MicroRNAs
Central Nervous System
Serum
Cytokines
Cerebral Ventricles
Endotoxemia
Microglia
High Fat Diet
Neurodegenerative Diseases
Tail
Veins
Immune System
Communication
Gene Expression
Messenger RNA
Injections

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. / Li, Jing Jing; Wang, Bin; Kodali, Mahesh Chandra; Chen, Chao; Kim, Eunhee; Patters, Benjamin John; Lan, Lubin; Kumar, Santosh; Wang, Xinjun; Yue, Junming; Liao, Francesca-Fang.

In: Journal of Neuroinflammation, Vol. 15, No. 1, 8, 08.01.2018.

Research output: Contribution to journalArticle

Li, Jing Jing ; Wang, Bin ; Kodali, Mahesh Chandra ; Chen, Chao ; Kim, Eunhee ; Patters, Benjamin John ; Lan, Lubin ; Kumar, Santosh ; Wang, Xinjun ; Yue, Junming ; Liao, Francesca-Fang. / In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. In: Journal of Neuroinflammation. 2018 ; Vol. 15, No. 1.
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AU - Patters, Benjamin John

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