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Title: General Anesthetics Inhibit LPS-Induced IL-1β Expression in Glial Cells.
Authors: Tanaka, Tomoharu  kyouindb  KAKEN_id
Kai, Shinichi
Matsuyama, Tomonori
Adachi, Takehiko
Fukuda, Kazuhiko  kyouindb  KAKEN_id
Hirota, Kiichi
Author's alias: 田中, 具治
Issue Date: 11-Dec-2013
Publisher: Public Library of Science
Journal title: PloS one
Volume: 8
Issue: 12
Thesis number: e82930
Abstract: [Background]Glial cells, including microglia and astrocytes, are considered the primary source of proinflammatory cytokines in the brain. Immune insults stimulate glial cells to secrete proinflammatory cytokines that modulate the acute systemic response, which includes fever, behavioral changes, and hypothalamic-pituitary-adrenal (HPA) axis activation. We investigated the effect of general anesthetics on proinflammatory cytokine expression in the primary cultured glial cells, the microglial cell line BV-2, the astrocytic cell line A-1 and mouse brain. [Methodology/Principal Findings]Primary cultured glial cells were exposed to lipopolysaccharide (LPS) in combination with general anesthetics including isoflurane, pentobarbital, midazolam, ketamine, and propofol. Following this treatment, we examined glial cell expression of the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α). LPS-induced expression of IL-1β mRNA and protein were significantly reduced by all the anesthetics tested, whereas IL-6 and TNF-α mRNA expression was unaffected. The anesthetics suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation, but did not affect nuclear factor-kappaB and activator protein-1 activation. The same effect was observed with BV-2, but not with A-1 cells. In the mouse experiments, LPS was injected intraperitoneally, and isoflurane suppressed IL-1β in the brain and adrenocorticotropic hormone in plasma, but not IL-1β in plasma. [Conclusions/Significance]Taken together, our results indicate that general anesthetics inhibit LPS-induced IL-1β upregulation in glial cells, particularly microglia, and affects HPA axis participation in the stress response.
Rights: © 2013 Tanaka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1371/journal.pone.0082930
PubMed ID: 24349401
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