Reference - Detail
|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.|
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.
|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|
|Human and Animal Cells||MG6(RCB2403)|