RRC ID 59721
Author Inoue T, Yamakage H, Tanaka M, Kusakabe T, Shimatsu A, Satoh-Asahara N.
Title Oxytocin Suppresses Inflammatory Responses Induced by Lipopolysaccharide through Inhibition of the eIF-2-ATF4 Pathway in Mouse Microglia.
Journal Cells
Abstract 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.
Volume 8(6)
Published 2019-5-31
DOI 10.3390/cells8060527
PII cells8060527
PMID 31159306
PMC PMC6627458
MeSH Activating Transcription Factor 4 / metabolism* Animals Cell Line Cytokines / biosynthesis Endoplasmic Reticulum Stress / drug effects Eukaryotic Initiation Factor-2 / metabolism* Inflammasomes / drug effects Inflammasomes / metabolism Inflammation / metabolism* Inflammation / pathology* Inflammation Mediators / metabolism Lipopolysaccharides Mice Microglia / drug effects Microglia / metabolism Microglia / pathology* 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
IF 5.656
Times Cited 4
Human and Animal Cells MG6(RCB2403)