Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation.
Biomarkers
Cytokines
/ metabolism
Disease Susceptibility
Fibroblasts
/ metabolism
Fluorescent Antibody Technique
Humans
Inflammasomes
/ metabolism
Inflammation Mediators
/ metabolism
Interleukin-1beta
/ metabolism
NF-kappa B
/ metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Protein Transport
Rett Syndrome
/ etiology
ASC
Cytokines
Inflammatory status
MeCP2
NLRP3
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
04
09
2019
revised:
23
09
2019
accepted:
26
09
2019
pubmed:
14
10
2019
medline:
22
9
2020
entrez:
14
10
2019
Statut:
ppublish
Résumé
Rett syndrome (RTT) is a progressive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene. RTT patients show multisystem disturbances associated with an oxinflammatory status. Inflammasomes are multi-protein complexes, responsible for host immune responses against pathogen infections and redox-related cellular stress. Assembly of NLRP3/ASC inflammasome triggers pro-caspase-1 activation, thus, resulting in IL-1β and IL-18 maturation. However, an aberrant activation of inflammasome system has been implicated in several human diseases. Our aim was to investigate the possible role of inflammasome in the chronic subclinical inflammatory condition typical of RTT, by analyzing this complex in basal and lipopolysaccharide (LPS)+ATP-stimulated primary fibroblasts, as well as in serum from RTT patients and healthy volunteers. RTT cells showed increased levels of nuclear p65 and ASC proteins, pro-IL-1β mRNA, and NLRP3/ASC interaction in basal condition, without any further response upon the LPS + ATP stimuli. Moreover, augmented levels of circulating ASC and IL-18 proteins were found in serum of RTT patients, which are likely able to amplify the inflammatory response. Taken together, our findings suggest that RTT patients exhibited a challenged inflammasome machinery at cellular and systemic level, which may contribute to the subclinical inflammatory state feedback observed in this pathology.
Identifiants
pubmed: 31606551
pii: S2213-2317(19)31060-2
doi: 10.1016/j.redox.2019.101334
pmc: PMC6812177
pii:
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
IL1B protein, human
0
Inflammasomes
0
Inflammation Mediators
0
Interleukin-1beta
0
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101334Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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