IL-17 signalling in astrocytes promotes glutamate excitotoxicity: Indications for the link between inflammatory and neurodegenerative events in multiple sclerosis.
Mult Scler Relat Disord
; 11: 12-17, 2017 Jan.
Article
en En
| MEDLINE
| ID: mdl-28104249
ABSTRACT
OBJECTIVE:
Th-17 cells have been exclusively referred to inflammatory events in multiple sclerosis (MS), while their importance in the development of glutamate excitotoxicity and the consequent neurodegeneration has been a completely unexplored concept. Accordingly, the objective of our study was to assess IL-17A effect on astrocyte ability to metabolize and release glutamate, considering that astrocytes had the central role in glutamate homeostasis.METHODS:
By using primary rat astrocyte cultures, astrocyte ability to uptake glutamate was estimated by the alterations of glutamate transporters (GLAST and GLT-1) expression, whereas changes in glutamine synthetase expression were used to estimate the ability to metabolize glutamate. Gene expression was determined by real time polymerase chain reaction (rtPCR). IL-17A effect on astrocyte ability to produce glutamate was investigated directly, by measuring the level of released glutamate using high performance liquid chromatography (HPLC).RESULTS:
Lower concentrations of IL-17A reduced the expressions of both glutamate transporters and glutamine synthetase; however, this effect was lost when IL-17A was applied in a higher dose. IL-17A did not significantly modify glutamate release from astrocyte in basal conditions, but following Ca2+ stimulation, as well as Ca2+ removal from the culture medium, IL-17A stimulated glutamate release in dose-dependent manner.CONCLUSION:
Together, these results support that IL-17A could promote glutamate excitotoxicity by decreasing astrocyte ability to uptake and convert glutamate to non-toxic glutamine, but also by stimulating Ca2+ dependent glutamate release. Such interactions between IL-17A and glutamate excitotoxicity implicate the potential link between inflammation and neurodegeneration during MS pathogenesis, and identify astrocytes as a potential target in achieving neuroprotective effects in MS.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Astrocitos
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Ácido Glutámico
/
Transportador 1 de Aminoácidos Excitadores
/
Transportador 2 de Aminoácidos Excitadores
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mult Scler Relat Disord
Año:
2017
Tipo del documento:
Article