title: Interferon-γ blocks signalling through PDGFRβ in human brain pericytes.
abstract: BACKGROUND
  Neuroinflammation and blood-brain barrier (BBB) disruption are common features of many brain disorders, including Alzheimer's disease, epilepsy, and motor neuron disease. Inflammation is thought to be a driver of BBB breakdown, but the underlying mechanisms for this are unclear. Brain pericytes are critical cells for maintaining the BBB and are immunologically active. We sought to test the hypothesis that inflammation regulates the BBB by altering pericyte biology.
  
  
  METHODS
  We exposed primary adult human brain pericytes to chronic interferon-gamma (IFNγ) for 4 days and measured associated functional aspects of pericyte biology. Specifically, we examined the influence of inflammation on platelet-derived growth factor receptor-beta (PDGFRβ) expression and signalling, as well as pericyte proliferation and migration by qRT-PCR, immunocytochemistry, flow cytometry, and western blotting.
  
  
  RESULTS
  Chronic IFNγ treatment had marked effects on pericyte biology most notably through the PDGFRβ, by enhancing agonist (PDGF-BB)-induced receptor phosphorylation, internalization, and subsequent degradation. Functionally, chronic IFNγ prevented PDGF-BB-mediated pericyte proliferation and migration.
  
  
  CONCLUSIONS
  Because PDGFRβ is critical for pericyte function and its removal leads to BBB leakage, our results pinpoint a mechanism linking chronic brain inflammation to BBB dysfunction.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 1023, Auckland, New Zealand.|Gravida National Centre for Growth and Development, The University of Auckland, 1023, Auckland, New Zealand.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: Deidre
authors.initials: D
authors.lastname: Jansson
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 1023, Auckland, New Zealand.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Scotter
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 1023, Auckland, New Zealand.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: Justin
authors.initials: J
authors.lastname: Rustenhoven
authors.affiliation: Department of Anatomy and Medical Imaging, The University of Auckland, 1023, Auckland, New Zealand.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: Natacha
authors.initials: N
authors.lastname: Coppieters
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 1023, Auckland, New Zealand.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: Leon C D
authors.initials: LC
authors.lastname: Smyth
authors.affiliation: Lab Plus, 1023, Auckland, New Zealand.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Oldfield
authors.affiliation: Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.|Auckland City Hospital, 1023, Auckland, New Zealand.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Bergin
authors.affiliation: Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.|Auckland City Hospital, 1023, Auckland, New Zealand.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Mee
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 1023, Auckland, New Zealand.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: E Scott
authors.initials: ES
authors.lastname: Graham
authors.affiliation: Department of Anatomy and Medical Imaging, The University of Auckland, 1023, Auckland, New Zealand.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 1023, Auckland, New Zealand. m.dragunow@auckland.ac.nz.|Gravida National Centre for Growth and Development, The University of Auckland, 1023, Auckland, New Zealand. m.dragunow@auckland.ac.nz.|Centre for Brain Research, The University of Auckland, 1023, Auckland, New Zealand. m.dragunow@auckland.ac.nz.|Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand. m.dragunow@auckland.ac.nz.
authors.forename: Mike
authors.initials: M
authors.lastname: Dragunow
keywords: Blood-brain barrier; Inflammation; Migration; Proliferation