University of Hertfordshire

Expression and functionality of P-glycoprotein in human bronchial epithelial cells in vitro

Research output: Contribution to journalMeeting abstract

  • Victoria Hutter
  • Constanze Hilgendorf
  • Anne Cooper
  • Vanessa Zann
  • David Pritchard
  • Cynthia Bosquillon
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Original languageEnglish
Article numberP843
Pages (from-to)142
JournalEuropean Respiratory Journal
Journal publication dateSep 2011
Volume38
IssueSupp 55
Publication statusPublished - Sep 2011
EventERS - Amsterdam, Netherlands
Duration: 24 Sep 201128 Sep 2011

Abstract

P-glycoprotein (P-gp) is expressed in normal tissues with barrier functions where it participates in cell defence mechanisms (Huls, M. et al. J Pharm Exp Ther 2009; 328:3-9). Its presence in the bronchial epithelium and role in the lung protection against inhaled toxicants has yet to be elucidated.
The human bronchial epithelial cell line Calu-3 and normal human bronchial epithelial (NHBE) cells were cultured at an air-liquid interface on Transwell® inserts for 21 days. P-gp expression was evaluated by quantitative polymerase chain reaction and its functionality was assessed by permeability measurements using the established substrate 3H-digoxin either alone or in the presence of chemical or biomolecular inhibitors.
P-gp was absent in NHBE cells and moderately expressed in Calu-3 cells. Net secretory transport of 3H-digoxin was observed in both models. This was reduced at 4°C and in the presence of the selective but non specific P-gp inhibitor PSC833 and the multidrug resistance protein (MRP) inhibitor MK571. The P-gp specific antibody inhibitor UIC2 and the metabolic inhibitors sodium azide and sodium dichloroacetate had no effect on 3H-digoxin transport in Calu-3 cells.
The presence of active transport mechanisms in cultures of human bronchial epithelial cells was demonstrated, although they differed between the models tested. P-gp was not detected in NHBE cells, in line with observed low gene expression in human lung tissue (Bleasby, K. et al. Xenobiotica 2006; 36:963-988). The involvement of P-gp could not be confirmed and the transporter(s) responsible for 3H-digoxin asymmetric broncho-epithelial permeability remain(s) to be identified.

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