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

van der Deen, M., Homan, S., Timmer-Bosscha, H., Scheper, R. J., Timens, W., Postma, D. S. & de Vries, E. G., 12-Sep-2008, In : International Journal of Chronic Obstructive Pulmonary Disease. 3, 3, p. 469-475 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)469-475
Number of pages7
JournalInternational Journal of Chronic Obstructive Pulmonary Disease
Volume3
Issue number3
Publication statusPublished - 12-Sep-2008

    Keywords

  • Acetylcysteine, Biological Transport, Bronchi, Bronchodilator Agents, Budesonide, Cholinergic Antagonists, Drug Resistance, Multiple, Epithelial Cells, Ethanolamines, Expectorants, Flow Cytometry, Humans, Ipratropium, Multidrug Resistance-Associated Proteins, Oxidative Stress, Pulmonary Disease, Chronic Obstructive

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