The metabolic response to inflammation in astrocytes is regulated by nuclear factor-kappa B signaling
dc.contributor.author | Robb, JL | |
dc.contributor.author | Hammad, NA | |
dc.contributor.author | Weightman Potter, PG | |
dc.contributor.author | Chilton, JK | |
dc.contributor.author | Beall, C | |
dc.contributor.author | Ellacott, KLJ | |
dc.date.accessioned | 2020-04-16T07:51:36Z | |
dc.date.issued | 2020-04-10 | |
dc.description.abstract | Inflammation and metabolism are intrinsically linked with inflammatory stimuli inducing metabolic changes in cells and, in turn, metabolic capacity determining cellular inflammatory responses. Although well characterized in peripheral immune cells there is comparatively less known about these “immunometabolic” responses in astrocytes. In this study, we tested the hypothesis that the astrocytic inflammatory response driven by nuclear factor‐kappa B (NF‐κB) signaling is dependent on glycolytic metabolism. Using mouse primary cortical astrocyte cultures, we assessed changes in cellular metabolism after exposure to lipopolysaccharide (LPS), with cytokine ELISAs and immunoblotting being used to measure inflammatory responses. Results indicate temporally distinct metabolic adaptations to pro‐inflammatory stimulation in astrocytes: 3 hr LPS treatment increased glycolysis but did not alter mitochondrial metabolism, while following 24 hr of LPS treatment we observed increased oxidative phosphorylation, and decreased glycolytic capacity and glucose uptake, partly due to reduced glucose transporter 1 expression. Inhibition of NF‐κB signaling with the IKK‐beta inhibitor TPCA‐1 prevented the LPS induced changes to glycolysis and oxidative phosphorylation. Furthermore, TPCA‐1 treatment altered both glycolysis and oxidative phosphorylation independently from inflammatory stimulation, indicating a role for NF‐κB signaling in regulation of basal metabolism in astrocytes. Inhibition of glycolysis with 2‐deoxyglucose significantly attenuated LPS‐induced cytokine release and NF‐κB phosphorylation, indicating that intact glycolysis is required for the full inflammatory response to LPS. Together our data indicate that astrocytes display immunometabolic responses to acute LPS stimulation which may represent a potential therapeutic target for neuroinflammatory disorders. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | European Foundation for the Study of Diabetes | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | European Foundation for the Study of Diabetes | en_GB |
dc.description.sponsorship | University of Exeter Medical School | en_GB |
dc.identifier.citation | Published online 10 April 2020 | en_GB |
dc.identifier.doi | 10.1002/glia.23835 | |
dc.identifier.grantnumber | 1-INO-2016-214-A-N | en_GB |
dc.identifier.grantnumber | 13/0004647 | en_GB |
dc.identifier.grantnumber | MR/N012763/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/120655 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley | en_GB |
dc.rights | © 2020 The Authors. Glia published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | astrocyte | en_GB |
dc.subject | glycolysis | en_GB |
dc.subject | Inflammation | en_GB |
dc.subject | metabolism | en_GB |
dc.subject | nuclear factor-kappa B | en_GB |
dc.title | The metabolic response to inflammation in astrocytes is regulated by nuclear factor-kappa B signaling | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-04-16T07:51:36Z | |
dc.identifier.issn | 0894-1491 | |
dc.description | This is the final version. Available from Wiley via the DOI in this record. | en_GB |
dc.description | The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. | en_GB |
dc.identifier.journal | Glia | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-03-31 | |
exeter.funder | ::Medical Research Council (MRC) | en_GB |
exeter.funder | ::European Foundation for the Study of Diabetes | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-03-31 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-04-16T07:47:30Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-04-16T07:51:39Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2020 The Authors. Glia published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.