Oxytocin Suppresses Inflammatory Responses Induced by Lipopolysaccharide through Inhibition of the eIF-2-ATF4 Pathway in Mouse Microglia.
Activating Transcription Factor 4
/ metabolism
Animals
Cell Line
Cytokines
/ biosynthesis
Endoplasmic Reticulum Stress
/ drug effects
Eukaryotic Initiation Factor-2
/ metabolism
Inflammasomes
/ drug effects
Inflammation
/ metabolism
Inflammation Mediators
/ metabolism
Lipopolysaccharides
Mice
Microglia
/ drug effects
NF-kappa B
/ metabolism
Oxytocin
/ pharmacology
Phosphorylation
/ drug effects
Protein Tyrosine Phosphatase, Non-Receptor Type 1
/ metabolism
Signal Transduction
/ drug effects
p38 Mitogen-Activated Protein Kinases
/ metabolism
endoplasmic reticulum stress
inflammasome
inflammation
microglia
oxytocin
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
31 05 2019
31 05 2019
Historique:
received:
13
05
2019
revised:
27
05
2019
accepted:
28
05
2019
entrez:
5
6
2019
pubmed:
5
6
2019
medline:
5
6
2019
Statut:
epublish
Résumé
Microglia maintain brain homeostasis and modulate neuroinflammation and are implicated in the pathogenesis of various neurological diseases such as Alzheimer's disease. In this study, we found that in lipopolysaccharide (LPS)-stimulated microglia, the endoplasmic reticulum (ER) stress-related eIF-2-ATF4 pathway plays significant roles in TNF- and IL-6 production, as well as in the inflammasome-mediated production of IL-1. Furthermore, our analysis revealed that oxytocin (OT), a nonapeptide synthesized in the hypothalamus, suppressed the production of these proinflammatory cytokines by inhibiting activation of the eIF-2-ATF4 pathway. Our findings therefore suggest a novel anti-inflammatory axis of OT in activated microglia, which would be helpful for developing the novel effective strategies for regulating microglia-associated neuroinflammation.
Identifiants
pubmed: 31159306
pii: cells8060527
doi: 10.3390/cells8060527
pmc: PMC6627458
pii:
doi:
Substances chimiques
Atf4 protein, mouse
0
Cytokines
0
Eukaryotic Initiation Factor-2
0
Inflammasomes
0
Inflammation Mediators
0
Lipopolysaccharides
0
NF-kappa B
0
Activating Transcription Factor 4
145891-90-3
Oxytocin
50-56-6
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Protein Tyrosine Phosphatase, Non-Receptor Type 1
EC 3.1.3.48
Ptpn1 protein, mouse
EC 3.1.3.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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