Tollip, an early regulator of the acute inflammatory response in the substantia nigra.

Détails

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Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_637444BCA5E2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tollip, an early regulator of the acute inflammatory response in the substantia nigra.
Périodique
Journal of neuroinflammation
Auteur⸱e⸱s
Humbert-Claude M., Duc D., Dwir D., Thieren L., Sandström von Tobel J., Begka C., Legueux F., Velin D., Maillard M.H., Do K.Q., Monnet-Tschudi F., Tenenbaum L.
ISSN
1742-2094 (Electronic)
ISSN-L
1742-2094
Statut éditorial
Publié
Date de publication
07/12/2016
Peer-reviewed
Oui
Volume
13
Numéro
1
Pages
303
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish

Résumé
Tollip is a ubiquitously expressed protein, originally described as a modulator of the IL-1R/TLR-NF-κB signaling pathways. Although this property has been well characterized in peripheral cells, and despite some evidence of its expression in the central nervous system, the role of Tollip in neuroinflammation remains poorly understood. The present study sought to explore the implication of Tollip in inflammation in the substantia nigra pars compacta, the structure affected in Parkinson's disease.
We first investigated Tollip distribution in the midbrain by immunohistochemistry. Then, we addressed TLR4-mediated response by intra-nigral injections of lipopolysaccharide (LPS), a TLR4 agonist, on inflammatory markers in Tollip knockout (KO) and wild-type (WT) mice.
We report an unexpectedly high Tollip immunostaining in dopaminergic neurons of the mice brain. Second, intra-nigral injection of LPS led to increased susceptibility to neuroinflammation in Tollip KO compared to Tollip WT mice. This was demonstrated by a significant increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and interferon gamma (IFN-γ) messenger RNA (mRNA) in the midbrain of Tollip KO mice upon LPS injection. Consistently, brain rAAV viral vector transduction with a nuclear factor kappa B (NF-κB)-inducible reporter gene confirmed increased NF-κB activation in Tollip KO mice. Lastly, Tollip KO mice displayed higher inducible NO synthase (iNOS) production, both at the messenger and protein level when compared to LPS-injected WT mice. Tollip deletion also aggravated LPS-induced oxidative and nitrosative damages, as indicated by an increase of 8-oxo-2'-deoxyguanosine and nitrotyrosine immunostaining, respectively.
Altogether, these findings highlight a critical role of Tollip in the early phase of TLR4-mediated neuroinflammation. As brain inflammation is known to contribute to Parkinson's disease, Tollip may be a potential target for neuroprotection.

Pubmed
Web of science
Open Access
Oui
Création de la notice
12/12/2016 13:37
Dernière modification de la notice
20/08/2019 14:20
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