Inflammation leads to distinct populations of extracellular vesicles from microglia

Autor: Christopher J.R. Dunning, Tomas Deierborg, Bettina Hjelm Clausen, Yiyi Yang, Antonio Boza-Serrano, Kate Lykke Lambertsen
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Lipopolysaccharides
Male
Lipopolysaccharide
medicine.medical_treatment
TNF
Gene Expression Regulation/drug effects
Nitric Oxide Synthase Type II
lcsh:RC346-429
Etanercept
chemistry.chemical_compound
Mice
Neuroinflammation
Signal Transduction/drug effects
Microglia/drug effects
Cell Line
Transformed
Mice
Knockout
medicine.diagnostic_test
Microglia
General Neuroscience
Cytokines/metabolism
Etanercept/pharmacology
Interleukin
Infarction
Middle Cerebral Artery
Cell biology
Protein Transport
Cytokine
medicine.anatomical_structure
Neurology
Cytokines
Tumor necrosis factor alpha
medicine.symptom
Nitric Oxide Synthase Type II/metabolism
Immunosuppressive Agents
Signal Transduction
Inflammation/etiology
Immunology
Inflammation
03 medical and health sciences
Cellular and Molecular Neuroscience
Extracellular Vesicles
Western blot
medicine
Animals
Infarction
Middle Cerebral Artery/complications
lcsh:Neurology. Diseases of the nervous system
Immunosuppressive Agents/pharmacology
Tumor Necrosis Factor-alpha
Research
Lipopolysaccharides/pharmacology
Protein Transport/drug effects
Mice
Inbred C57BL
Extracellular Vesicles/pathology
Disease Models
Animal
030104 developmental biology
chemistry
Gene Expression Regulation
Tumor Necrosis Factor-alpha/deficiency
Extracellular vesicles (EVs)
Zdroj: Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-19 (2018)
Journal of Neuroinflammation
Yang, Y, Boza-Serrano, A, Dunning, C J R, Clausen, B H, Lambertsen, K L & Deierborg, T 2018, ' Inflammation leads to distinct populations of extracellular vesicles from microglia ', Journal of Neuroinflammation, vol. 15, 168 . https://doi.org/10.1186/s12974-018-1204-7
ISSN: 1742-2094
DOI: 10.1186/s12974-018-1204-7
Popis: Background Activated microglia play an essential role in inflammatory responses elicited in the central nervous system (CNS). Microglia-derived extracellular vesicles (EVs) are suggested to be involved in propagation of inflammatory signals and in the modulation of cell-to-cell communication. However, there is a lack of knowledge on the regulation of EVs and how this in turn facilitates the communication between cells in the brain. Here, we characterized microglial EVs under inflammatory conditions and investigated the effects of inflammation on the EV size, quantity, and protein content. Methods We have utilized western blot, nanoparticle tracking analysis (NTA), and mass spectrometry to characterize EVs and examine the alterations of secreted EVs from a microglial cell line (BV2) following lipopolysaccharide (LPS) and tumor necrosis factor (TNF) inhibitor (etanercept) treatments, or either alone. The inflammatory responses were measured with multiplex cytokine ELISA and western blot. We also subjected TNF knockout mice to experimental stroke (permanent middle cerebral artery occlusion) and validated the effect of TNF inhibition on EV release. Results Our analysis of EVs originating from activated BV2 microglia revealed a significant increase in the intravesicular levels of TNF and interleukin (IL)-6. We also observed that the number of EVs released was reduced both in vitro and in vivo when inflammation was inhibited via the TNF pathway. Finally, via mass spectrometry, we identified 49 unique proteins in EVs released from LPS-activated microglia compared to control EVs (58 proteins in EVs released from LPS-activated microglia and 37 from control EVs). According to Gene Ontology (GO) analysis, we found a large increase of proteins related to translation and transcription in EVs from LPS. Importantly, we showed a distinct profile of proteins found in EVs released from LPS treated cells compared to control. Conclusions We demonstrate altered EV production in BV2 microglial cells and altered cytokine levels and protein composition carried by EVs in response to LPS challenge. Our findings provide new insights into the potential roles of EVs that could be related to the pathogenesis in neuroinflammatory diseases. Electronic supplementary material The online version of this article (10.1186/s12974-018-1204-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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