Microglia are both a source and target of extracellular cyclophilin A

Gurkiran Kaur Flora, Ryan S. Anderton, Bruno P. Meloni, Gilles J. Guillemin, Neville W. Knuckey, Gabriella MacDougall, Vance Matthews, Sherif Boulos

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

LanguageEnglish
Article numbere02390
Pages1-8
Number of pages8
JournalHeliyon
Volume5
Issue number9
DOIs
Publication statusPublished - 1 Sep 2019

Fingerprint

Cyclophilin A
Microglia
Glioblastoma
Chemokines
Oxidative Stress
6-anilino-5,8-quinolinedione
Tumor Microenvironment
Cell Surface Receptors
Chemotaxis
Cellular Structures
Endotoxins
Brain Neoplasms
Wound Healing
Lipopolysaccharides
Interleukin-6
Cell Survival
Cell Death
Western Blotting
Enzyme-Linked Immunosorbent Assay
Phosphorylation

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Biochemistry
  • CD147
  • Cyclophilin A
  • Glioblastoma
  • Immunology
  • Inflammation
  • Microglia
  • Neurology
  • Neuroscience
  • Oxidative stress
  • Proteins

Cite this

Flora, G. K., Anderton, R. S., Meloni, B. P., Guillemin, G. J., Knuckey, N. W., MacDougall, G., ... Boulos, S. (2019). Microglia are both a source and target of extracellular cyclophilin A. Heliyon, 5(9), 1-8. [e02390]. https://doi.org/10.1016/j.heliyon.2019.e02390
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. In: Heliyon. 2019 ; Vol. 5, No. 9. pp. 1-8.
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abstract = "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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Flora, GK, Anderton, RS, Meloni, BP, Guillemin, GJ, Knuckey, NW, MacDougall, G, Matthews, V & Boulos, S 2019, 'Microglia are both a source and target of extracellular cyclophilin A', Heliyon, vol. 5, no. 9, e02390, pp. 1-8. https://doi.org/10.1016/j.heliyon.2019.e02390

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.

In: Heliyon, Vol. 5, No. 9, e02390, 01.09.2019, p. 1-8.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Flora, Gurkiran Kaur

AU - Anderton, Ryan S.

AU - Meloni, Bruno P.

AU - Guillemin, Gilles J.

AU - Knuckey, Neville W.

AU - MacDougall, Gabriella

AU - Matthews, Vance

AU - Boulos, Sherif

N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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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KW - Biochemistry

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KW - Neurology

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Flora GK, Anderton RS, Meloni BP, Guillemin GJ, Knuckey NW, MacDougall G et al. Microglia are both a source and target of extracellular cyclophilin A. Heliyon. 2019 Sep 1;5(9):1-8. e02390. https://doi.org/10.1016/j.heliyon.2019.e02390