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Flora GK, Anderton RS, Meloni BP, et al. Microglia are both a source and target of extracellular cyclophilin A. Heliyon. 2019;5(9):e02390doi: 10.1016/j.heliyon.2019.e02390.
Flora, G. K., Anderton, R. S., Meloni, B. P., Guillemin, G. J., Knuckey, N. W., MacDougall, G., Matthews, V., & Boulos, S. (2019). Microglia are both a source and target of extracellular cyclophilin A. Heliyon, 5(9), e02390. https://doi.org/10.1016/j.heliyon.2019.e02390
Flora, Gurkiran Kaur, et al. "Microglia are both a source and target of extracellular cyclophilin A." Heliyon vol. 5,9 (2019): e02390. doi: https://doi.org/10.1016/j.heliyon.2019.e02390
Flora GK, Anderton RS, Meloni BP, Guillemin GJ, Knuckey NW, MacDougall G, Matthews V, Boulos S. Microglia are both a source and target of extracellular cyclophilin A. Heliyon. 2019 Sep 03;5(9):e02390. doi: 10.1016/j.heliyon.2019.e02390. eCollection 2019 Sep. PMID: 31517118; PMCID: PMC6731207.
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Heliyon. 2019 Sep 03;5(9):e02390. doi: 10.1016/j.heliyon.2019.e02390. eCollection 2019 Sep.

Microglia are both a source and target of extracellular cyclophilin A.

Heliyon

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

Affiliations

  1. Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australia.
  2. Perron Institute for Neurological and Translational Sciences, QEII Medical Centre, Nedlands, Western Australia, Australia.
  3. School of Health Sciences and Institute for Health Research, Fremantle, University of Notre Dame Australia, Australia.
  4. Department of Neurosurgery, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia, Australia.
  5. Neuroinflammation Group, Faculty of Medicine and Health Sciences, 2 Technology Place, Macquarie University, New South Wales, Australia.
  6. School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia.

PMID: 31517118 PMCID: PMC6731207 DOI: 10.1016/j.heliyon.2019.e02390

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.

Keywords: Biochemistry; CD147; Cyclophilin A; Glioblastoma; Immunology; Inflammation; Microglia; Neurology; Neuroscience; Oxidative stress; Proteins

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