Unravelling the role of extracellular small heat-shock proteins in neuroinflammation

Background: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). During lesion development in MS, there is increased expression of small heat-shock proteins (HSPBs). The protective roles of HSPBs in regulating neural cell survival, inhibiting protein aggreg...

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Bibliographic Details
Published in:Journal of extracellular vesicles 2018-01, Vol.7, p.262-262
Main Authors: Vanherle, Sam, Van den Broek, Bram, De Winter, Vicky, Munuswamy, Revathy, Hosseinkhani, Baharak, Timmerman, Vincent, Michiels, Luc, Irobi, Joy
Format: Article
Language:English
Subjects:
Cell lines
Cell survival
Central nervous system
Demyelination
Heat shock proteins
Hsp70 protein
Inflammation
Intercellular adhesion molecule 1
Microglia
Multiple sclerosis
Protein interaction
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Summary:Background: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). During lesion development in MS, there is increased expression of small heat-shock proteins (HSPBs). The protective roles of HSPBs in regulating neural cell survival, inhibiting protein aggregation and regulating inflammation in the CNS is well known. Nonetheless, the extracellular role of HSPBs in neuroinflammation is unclear. One way that HSPBs are released into the extracellular space is through extracellular vesicles (EV). During neuroinflammation, neural cells (microglia and oligodendrocyte) release EVs either carrying beneficial or detrimental biomarkers into the environment. Here, we characterize the neural cells derived-EV and hypothesize that impaired EV expression can disrupt cell survival communications during neuroinflammation. Methods: The role of HSPB-EV in inflammation is investigated in two steps. (1) Establish HSPBs expressing neural cell lines for the production of HSPB-EV. (2) Isolation and characterization of EV using different techniques. Results: NTA measurement of microglial derived-EV showed an increased EV secretion upon inflammation. Stable HSPBs expressing cell derived-EV revealed a decrease in EV release during inflammation. SPR analysis of oligodendrocyte derived-EV showed interactions with ICAM1 and HSP70. In addition, immunoblot analysis of oligodendrocyte derived-EV showed a downregulation of monomeric HSPB8 and phosphorylated HSPB1 during inflammation. Summary/Conclusion: Neural cells derived-EVs constitutively express HSPB1 and HSPB8. However upon inflammation, there is a downregulation of both the monomeric forms as well as the phosphorylated HSPB1. This study shows that reduced expression in the extracellular HSPB1/B8-EV upon neuroinflammation can impair neural cell survival signalling.
ISSN:2001-3078