PortalPublikationenPI3Kδ inhibition reduces TNF secretion and neuroinflammation...

PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model

Standard

PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model. / Low, Pei Ching; Manzanero, Silvia; Mohannak, Nika; Narayana, Vinod K; Nguyen, Tam H; Kvaskoff, David; Brennan, Faith H; Ruitenberg, Marc J; Gelderblom, Mathias; Magnus, Tim; Kim, Hyun Ah; Broughton, Brad R S; Sobey, Christopher G; Vanhaesebroeck, Bart; Stow, Jennifer L; Arumugam, Thiruma V; Meunier, Frédéric A.

in: NAT COMMUN, Jahrgang 5, 2014, S. 3450.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Low, PC, Manzanero, S, Mohannak, N, Narayana, VK, Nguyen, TH, Kvaskoff, D, Brennan, FH, Ruitenberg, MJ, Gelderblom, M, Magnus, T, Kim, HA, Broughton, BRS, Sobey, CG, Vanhaesebroeck, B, Stow, JL, Arumugam, TV & Meunier, FA 2014, 'PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model', NAT COMMUN, Jg. 5, S. 3450. https://doi.org/10.1038/ncomms4450

APA

Low, P. C., Manzanero, S., Mohannak, N., Narayana, V. K., Nguyen, T. H., Kvaskoff, D., Brennan, F. H., Ruitenberg, M. J., Gelderblom, M., Magnus, T., Kim, H. A., Broughton, B. R. S., Sobey, C. G., Vanhaesebroeck, B., Stow, J. L., Arumugam, T. V., & Meunier, F. A. (2014). PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model. NAT COMMUN, 5, 3450. https://doi.org/10.1038/ncomms4450

Vancouver

Low PC, Manzanero S, Mohannak N, Narayana VK, Nguyen TH, Kvaskoff D et al. PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model. NAT COMMUN. 2014;5:3450. https://doi.org/10.1038/ncomms4450

Bibtex

@article{063ded794f0f49a8b770af890c11c7d4,
title = "PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model",
abstract = "Stroke is a major cause of death worldwide and the leading cause of permanent disability. Although reperfusion is currently used as treatment, the restoration of blood flow following ischaemia elicits a profound inflammatory response mediated by proinflammatory cytokines such as tumour necrosis factor (TNF), exacerbating tissue damage and worsening the outcomes for stroke patients. Phosphoinositide 3-kinase delta (PI3Kδ) controls intracellular TNF trafficking in macrophages and therefore represents a prospective target to limit neuroinflammation. Here we show that PI3Kδ inhibition confers protection in ischaemia/reperfusion models of stroke. In vitro, restoration of glucose supply following an episode of glucose deprivation potentiates TNF secretion from primary microglia-an effect that is sensitive to PI3Kδ inhibition. In vivo, transient middle cerebral artery occlusion and reperfusion in kinase-dead PI3Kδ (p110δ(D910A/D910A)) or wild-type mice pre- or post-treated with the PI3Kδ inhibitor CAL-101, leads to reduced TNF levels, decreased leukocyte infiltration, reduced infarct size and improved functional outcome. These data identify PI3Kδ as a potential therapeutic target in ischaemic stroke.",
author = "Low, {Pei Ching} and Silvia Manzanero and Nika Mohannak and Narayana, {Vinod K} and Nguyen, {Tam H} and David Kvaskoff and Brennan, {Faith H} and Ruitenberg, {Marc J} and Mathias Gelderblom and Tim Magnus and Kim, {Hyun Ah} and Broughton, {Brad R S} and Sobey, {Christopher G} and Bart Vanhaesebroeck and Stow, {Jennifer L} and Arumugam, {Thiruma V} and Meunier, {Fr{\'e}d{\'e}ric A}",
year = "2014",
doi = "10.1038/ncomms4450",
language = "English",
volume = "5",
pages = "3450",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model

AU - Low, Pei Ching

AU - Manzanero, Silvia

AU - Mohannak, Nika

AU - Narayana, Vinod K

AU - Nguyen, Tam H

AU - Kvaskoff, David

AU - Brennan, Faith H

AU - Ruitenberg, Marc J

AU - Gelderblom, Mathias

AU - Magnus, Tim

AU - Kim, Hyun Ah

AU - Broughton, Brad R S

AU - Sobey, Christopher G

AU - Vanhaesebroeck, Bart

AU - Stow, Jennifer L

AU - Arumugam, Thiruma V

AU - Meunier, Frédéric A

PY - 2014

Y1 - 2014

N2 - Stroke is a major cause of death worldwide and the leading cause of permanent disability. Although reperfusion is currently used as treatment, the restoration of blood flow following ischaemia elicits a profound inflammatory response mediated by proinflammatory cytokines such as tumour necrosis factor (TNF), exacerbating tissue damage and worsening the outcomes for stroke patients. Phosphoinositide 3-kinase delta (PI3Kδ) controls intracellular TNF trafficking in macrophages and therefore represents a prospective target to limit neuroinflammation. Here we show that PI3Kδ inhibition confers protection in ischaemia/reperfusion models of stroke. In vitro, restoration of glucose supply following an episode of glucose deprivation potentiates TNF secretion from primary microglia-an effect that is sensitive to PI3Kδ inhibition. In vivo, transient middle cerebral artery occlusion and reperfusion in kinase-dead PI3Kδ (p110δ(D910A/D910A)) or wild-type mice pre- or post-treated with the PI3Kδ inhibitor CAL-101, leads to reduced TNF levels, decreased leukocyte infiltration, reduced infarct size and improved functional outcome. These data identify PI3Kδ as a potential therapeutic target in ischaemic stroke.

AB - Stroke is a major cause of death worldwide and the leading cause of permanent disability. Although reperfusion is currently used as treatment, the restoration of blood flow following ischaemia elicits a profound inflammatory response mediated by proinflammatory cytokines such as tumour necrosis factor (TNF), exacerbating tissue damage and worsening the outcomes for stroke patients. Phosphoinositide 3-kinase delta (PI3Kδ) controls intracellular TNF trafficking in macrophages and therefore represents a prospective target to limit neuroinflammation. Here we show that PI3Kδ inhibition confers protection in ischaemia/reperfusion models of stroke. In vitro, restoration of glucose supply following an episode of glucose deprivation potentiates TNF secretion from primary microglia-an effect that is sensitive to PI3Kδ inhibition. In vivo, transient middle cerebral artery occlusion and reperfusion in kinase-dead PI3Kδ (p110δ(D910A/D910A)) or wild-type mice pre- or post-treated with the PI3Kδ inhibitor CAL-101, leads to reduced TNF levels, decreased leukocyte infiltration, reduced infarct size and improved functional outcome. These data identify PI3Kδ as a potential therapeutic target in ischaemic stroke.

U2 - 10.1038/ncomms4450

DO - 10.1038/ncomms4450

M3 - SCORING: Journal article

C2 - 24625684

VL - 5

SP - 3450

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -