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Open AccessArticle

Oxytocin Suppresses Inflammatory Responses Induced by Lipopolysaccharide through Inhibition of the eIF-2α–ATF4 Pathway in Mouse Microglia

1
Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
2
Department of Physical Therapy, Health Science University, Yamanashi 401-0380, Japan
3
Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
*
Author to whom correspondence should be addressed.
Cells 2019, 8(6), 527; https://doi.org/10.3390/cells8060527
Received: 13 May 2019 / Revised: 27 May 2019 / Accepted: 28 May 2019 / Published: 31 May 2019
(This article belongs to the Special Issue Microglia in Neurodegenerative Diseases)
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-2α–ATF4 pathway plays significant roles in TNF-α and IL-6 production, as well as in the inflammasome-mediated production of IL-1β. 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-2α–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. View Full-Text
Keywords: endoplasmic reticulum stress; inflammation; inflammasome; microglia; oxytocin endoplasmic reticulum stress; inflammation; inflammasome; microglia; oxytocin
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Inoue, T.; Yamakage, H.; Tanaka, M.; Kusakabe, T.; Shimatsu, A.; Satoh-Asahara, N. Oxytocin Suppresses Inflammatory Responses Induced by Lipopolysaccharide through Inhibition of the eIF-2α–ATF4 Pathway in Mouse Microglia. Cells 2019, 8, 527.

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