skip to content
Dovepress - Open Access to Scientific and Medical Research
View our mobile site

8850

Effect of COPD treatments on MRP1-mediated transport in bronchial epithelial cells

Original Research

(2532) Views  (574) Full article downloads

Authors: Margaretha van der Deen, Sandra Homan, Hetty Timmer-Bosscha, Rik J Scheper, Wim Timens, et al

Published Date October 2008 Volume 2008:3(3) Pages 469 - 475
DOI: http://dx.doi.org/10.2147/COPD.S2817

Margaretha van der Deen1, Sandra Homan1, Hetty Timmer-Bosscha1, Rik J Scheper2, Wim Timens3, Dirkje S Postma4, Elisabeth G de Vries1

Departments of 1Medical Oncology, 3Pathology, 4Pulmonary Diseases, University Medical Center Groningen and University of Groningen, The Netherlands; 2Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

Background: Smoking is the principle risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is known to protect against toxic compounds and oxidative stress, and might play a role in protection against smoke-induced disease progression. We questioned whether MRP1-mediated transport is influenced by pulmonary drugs that are commonly prescribed in COPD.

Methods: The immortalized human bronchial epithelial cell line 16HBE14o- was used to analyze direct in vitro effects of budesonide, formoterol, ipratropium bromide and N-acetylcysteine (NAC) on MRP1-mediated transport. Carboxyfluorescein (CF) was used as a model MRP1 substrate and was measured with functional flow cytometry.

Results: Formoterol had a minor effect, whereas budesonide concentration-dependently decreased CF transport by MRP1. Remarkably, addition of formoterol to the highest concentration of budesonide increased CF transport. Ipratropium bromide inhibited CF transport at low concentrations and tended to increase CF transport at higher levels. NAC increased CF transport by MRP1 in a concentration-dependent manner.

Conclusions: Our data suggest that, besides their positive effects on respiratory symptoms, budesonide, formoterol, ipratropium bromide, and NAC modulate MRP1 activity in bronchial epithelial cells. Further studies are required to assess whether stimulation of MRP1 activity is beneficial for long-term treatment of COPD.

Keywords: bronchus epithelium, COPD, drugs, MRP1, multidrug resistance, oxidative stress








Readers of this article also read:

Role of macrolide therapy in chronic obstructive pulmonary disease
Noninvasive ventilation in patients with chronic obstructive airway disease
Benefits of short inspiratory muscle training on exercise capacity, dyspnea, and inspiratory fraction in COPD patients
Mechanisms of improvement of respiratory failure in patients with COPD treated with NIV
Preferential recruitment of neutrophils by endothelin-1 in acute lung inflammation induced by lipopolysaccharide or cigarette smoke
Exacerbation rate, health status and mortality in COPD – a review of potential interventions
The pathophysiology of bronchiectasis
Budesonide/formoterol combination in COPD: a US perspective
Development and implementation of treadmill exercise testing protocols in COPD
Solid self-nanoemulsifying cyclosporin A pellets prepared by fluid-bed coating: preparation, characterization and in vitro redispersibility
  • Journal Indexing

    See where all the Dove Press journals are indexed

  • Testimonials

    "You do a tremendous job!!" Ruben Restrepo, The University of Texas Health Science Center at San Antonio