16HBE14o- human bronchial epithelial cell layers express P-glycoprotein, lung resistance-related protein, and caveolin-1

Pharm Res. 2003 Apr;20(4):545-51. doi: 10.1023/a:1023230328687.

Abstract

Purpose: To study the expression of P-glycoprotein (P-gp), lung resistance-related protein (LRP), and caveolin-1 (cav-1) in the human bronchial epithelial cell line 16HBE14o-.

Methods: The presence of P-gp, LRP, and cav-1 in 16HBE14o- cell layers was evaluated using immunocytochemical staining and visualization with confocal laser scanning microscopy (CLSM). Functionality of P-gp was determined by bidirectional transport of rhodamine-123 with and without a P-gp inhibitor, verapamil. Caveolae were visualized using transmission electron microscopy (TEM). Flux of fluorescein-Na was also studied as a paracellular transport marker.

Results: Immunocytochemical staining showed expression of P-gp localized at the apical membrane of 16HBE14o- cell layers. The flux of rhodamine 123 across cell layers exhibited a greater Papp value for the secretory (i.e., basolateral-to-apical) direction. This asymmetry disappeared in the presence of verapamil. CLSM provided evidence for the expression of LRP and cav-1. TEM further showed typically shaped caveolae at the apical and basolateral membranes.

Conclusion: Cell layers of 16HBE14o- express drug transport systems that are also present in the human bronchus in vivo, indicating that the 16HBE14o- cell line may be a suitable candidate for an in vitro model for mechanistic studies of drug transport processes involved in the smaller airways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Biological Transport / physiology
  • Bronchi / cytology*
  • Bronchi / metabolism*
  • Caveolin 1
  • Caveolins / metabolism*
  • Cell Line*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Humans
  • Models, Biological*
  • Neoplasm Proteins / metabolism*
  • Rabbits
  • Vault Ribonucleoprotein Particles / metabolism*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • CAV1 protein, human
  • Caveolin 1
  • Caveolins
  • Neoplasm Proteins
  • Vault Ribonucleoprotein Particles
  • major vault protein