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Microglia are both a source and target of extracellular cyclophilin A

Glioblastoma (GBM) are lethal primary brain tumours whose pathogenesis is aided, at least partly, via a pro-tumorigenic microenvironment. This study investigated whether microglia, a cell component of the GBM microenvironment, mediates pro-tumorigenic properties via the action of cyclophilin A (CypA...

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Autores principales: Flora, Gurkiran Kaur, Anderton, Ryan S., Meloni, Bruno P., Guillemin, Gilles J., Knuckey, Neville W., MacDougall, Gabriella, Matthews, Vance, Boulos, Sherif
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731207/
https://www.ncbi.nlm.nih.gov/pubmed/31517118
http://dx.doi.org/10.1016/j.heliyon.2019.e02390
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author Flora, Gurkiran Kaur
Anderton, Ryan S.
Meloni, Bruno P.
Guillemin, Gilles J.
Knuckey, Neville W.
MacDougall, Gabriella
Matthews, Vance
Boulos, Sherif
author_facet Flora, Gurkiran Kaur
Anderton, Ryan S.
Meloni, Bruno P.
Guillemin, Gilles J.
Knuckey, Neville W.
MacDougall, Gabriella
Matthews, Vance
Boulos, Sherif
author_sort Flora, Gurkiran Kaur
collection PubMed
description Glioblastoma (GBM) are lethal primary brain tumours whose pathogenesis is aided, at least partly, via a pro-tumorigenic microenvironment. This study investigated whether microglia, a cell component of the GBM microenvironment, mediates pro-tumorigenic properties via the action of cyclophilin A (CypA), a potent secretable chemokine and cytoprotectant that signals via the cell surface receptor, CD147. To this end, intracellular and secreted CypA expression was assessed in human primary microglia and BV2 microglial cells treated with the endotoxin, lipopolysaccharide (LPS) and the oxidative stress inducer, LY83583. We report that human primary microglia and BV2 microglia both express CypA and CD147, and that BV2 microglial cells secrete CypA in response to pro-inflammatory and oxidative stimuli. We also demonstrate for the first time that recombinant CypA (rCypA; 1nM–1000nM) dose-dependently increased wound healing and reduced basal cell death in BV2 microglial cells. To determine the cell–signalling pathways involved, we probed microglial cell lysates for changes in ERK1/2 and AKT phosphorylation, IκB degradation, and IL-6 secretion using Western blot and ELISA analysis. In summary, BV2 microglial cells secrete CypA in response to inflammatory and oxidative stress, and that rCypA increases cell viability and chemotaxis. Our findings suggest that rCypA is a pro-survival chemokine for microglia that may influence the GBM tumour microenvironment.
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spelling pubmed-67312072019-09-12 Microglia are both a source and target of extracellular cyclophilin A Flora, Gurkiran Kaur Anderton, Ryan S. Meloni, Bruno P. Guillemin, Gilles J. Knuckey, Neville W. MacDougall, Gabriella Matthews, Vance Boulos, Sherif Heliyon Article Glioblastoma (GBM) are lethal primary brain tumours whose pathogenesis is aided, at least partly, via a pro-tumorigenic microenvironment. This study investigated whether microglia, a cell component of the GBM microenvironment, mediates pro-tumorigenic properties via the action of cyclophilin A (CypA), a potent secretable chemokine and cytoprotectant that signals via the cell surface receptor, CD147. To this end, intracellular and secreted CypA expression was assessed in human primary microglia and BV2 microglial cells treated with the endotoxin, lipopolysaccharide (LPS) and the oxidative stress inducer, LY83583. We report that human primary microglia and BV2 microglia both express CypA and CD147, and that BV2 microglial cells secrete CypA in response to pro-inflammatory and oxidative stimuli. We also demonstrate for the first time that recombinant CypA (rCypA; 1nM–1000nM) dose-dependently increased wound healing and reduced basal cell death in BV2 microglial cells. To determine the cell–signalling pathways involved, we probed microglial cell lysates for changes in ERK1/2 and AKT phosphorylation, IκB degradation, and IL-6 secretion using Western blot and ELISA analysis. In summary, BV2 microglial cells secrete CypA in response to inflammatory and oxidative stress, and that rCypA increases cell viability and chemotaxis. Our findings suggest that rCypA is a pro-survival chemokine for microglia that may influence the GBM tumour microenvironment. Elsevier 2019-09-03 /pmc/articles/PMC6731207/ /pubmed/31517118 http://dx.doi.org/10.1016/j.heliyon.2019.e02390 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Flora, Gurkiran Kaur
Anderton, Ryan S.
Meloni, Bruno P.
Guillemin, Gilles J.
Knuckey, Neville W.
MacDougall, Gabriella
Matthews, Vance
Boulos, Sherif
Microglia are both a source and target of extracellular cyclophilin A
title Microglia are both a source and target of extracellular cyclophilin A
title_full Microglia are both a source and target of extracellular cyclophilin A
title_fullStr Microglia are both a source and target of extracellular cyclophilin A
title_full_unstemmed Microglia are both a source and target of extracellular cyclophilin A
title_short Microglia are both a source and target of extracellular cyclophilin A
title_sort microglia are both a source and target of extracellular cyclophilin a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731207/
https://www.ncbi.nlm.nih.gov/pubmed/31517118
http://dx.doi.org/10.1016/j.heliyon.2019.e02390
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