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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 RJ, Timens W, Postma DS, de Vries EG - Int J Chron Obstruct Pulmon Dis (2008)

Bottom Line: 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.Formoterol had a minor effect, whereas budesonide concentration-dependently decreased CF transport by MRP1.Our data suggest that, besides their positive effects on respiratory symptoms, budesonide, formoterol, ipratropium bromide, and NAC modulate MRP1 activity in bronchial epithelial cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands.

ABSTRACT

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.

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Related in: MedlinePlus

Modulation of MRP1-mediated activity with increasing concentrations of (A) budesonide or (B) formoterol. Dashed line indicates the MFI level of the control (incubation with vehicle). Data are shown of mean ± SEM of 3–4 independent experiments for budesonide and 5–6 independent experiments for formoterol. *p < 0.05 compared with control.Abbreviations: CF, carboxyfluorescein; MFI, mean fluorescence intensity; MRP1, multidrug resistance-associated protein 1.
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f1-copd-3-469: Modulation of MRP1-mediated activity with increasing concentrations of (A) budesonide or (B) formoterol. Dashed line indicates the MFI level of the control (incubation with vehicle). Data are shown of mean ± SEM of 3–4 independent experiments for budesonide and 5–6 independent experiments for formoterol. *p < 0.05 compared with control.Abbreviations: CF, carboxyfluorescein; MFI, mean fluorescence intensity; MRP1, multidrug resistance-associated protein 1.

Mentions: Budesonide increased the accumulation of CF at concentrations of 10−5 M and 10−4 M with 26% and 97%, respectively. Lower concentrations did not affect CF accumulation significantly (Figure 1A). Formoterol had a small yet significant effect on the accumulation of CF at 10−8 M, but at higher concentrations this effect was not significant (Figure 1B).


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

van der Deen M, Homan S, Timmer-Bosscha H, Scheper RJ, Timens W, Postma DS, de Vries EG - Int J Chron Obstruct Pulmon Dis (2008)

Modulation of MRP1-mediated activity with increasing concentrations of (A) budesonide or (B) formoterol. Dashed line indicates the MFI level of the control (incubation with vehicle). Data are shown of mean ± SEM of 3–4 independent experiments for budesonide and 5–6 independent experiments for formoterol. *p < 0.05 compared with control.Abbreviations: CF, carboxyfluorescein; MFI, mean fluorescence intensity; MRP1, multidrug resistance-associated protein 1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2629975&req=5

f1-copd-3-469: Modulation of MRP1-mediated activity with increasing concentrations of (A) budesonide or (B) formoterol. Dashed line indicates the MFI level of the control (incubation with vehicle). Data are shown of mean ± SEM of 3–4 independent experiments for budesonide and 5–6 independent experiments for formoterol. *p < 0.05 compared with control.Abbreviations: CF, carboxyfluorescein; MFI, mean fluorescence intensity; MRP1, multidrug resistance-associated protein 1.
Mentions: Budesonide increased the accumulation of CF at concentrations of 10−5 M and 10−4 M with 26% and 97%, respectively. Lower concentrations did not affect CF accumulation significantly (Figure 1A). Formoterol had a small yet significant effect on the accumulation of CF at 10−8 M, but at higher concentrations this effect was not significant (Figure 1B).

Bottom Line: 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.Formoterol had a minor effect, whereas budesonide concentration-dependently decreased CF transport by MRP1.Our data suggest that, besides their positive effects on respiratory symptoms, budesonide, formoterol, ipratropium bromide, and NAC modulate MRP1 activity in bronchial epithelial cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus