Effect of COPD Treatments on MRP1-mediated Transport in Bronchial Epithelial Cells

Overview

Journal Int J Chron Obstruct Pulmon Dis

Publisher Dove Medical Press

Specialty Pulmonary Medicine

Date 2008 Nov 11

PMID 18990976

Citations 9

Authors

Margaretha van der Deen

Sandra Homan

Hetty Timmer-Bosscha

Rik J Scheper

Wim Timens

Dirkje S Postma

Elisabeth G de Vries

Affiliations

Soon will be listed here.

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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References

Leslie E, Deeley R, Cole S . Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters. Toxicology. 2001; 167(1):3-23. DOI: 10.1016/s0300-483x(01)00454-1. View

Gillissen A, Jaworska M, Orth M, Coffiner M, Maes P, App E . Nacystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro. Respir Med. 1997; 91(3):159-68. DOI: 10.1016/s0954-6111(97)90052-4. View

Scheffer G, Pijnenborg A, Smit E, Muller M, Postma D, Timens W . Multidrug resistance related molecules in human and murine lung. J Clin Pathol. 2002; 55(5):332-9. PMC: 1769658. DOI: 10.1136/jcp.55.5.332. View

van der Deen M, Marks H, Willemse B, Postma D, Muller M, Smit E . Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients. Virchows Arch. 2006; 449(6):682-8. DOI: 10.1007/s00428-006-0240-3. View

Sutherland E, Allmers H, Ayas N, Venn A, Martin R . Inhaled corticosteroids reduce the progression of airflow limitation in chronic obstructive pulmonary disease: a meta-analysis. Thorax. 2003; 58(11):937-41. PMC: 1746510. DOI: 10.1136/thorax.58.11.937. View

Bagrij T, Klokouzas A, HLADKY S, Barrand M . Influences of glutathione on anionic substrate efflux in tumour cells expressing the multidrug resistance-associated protein, MRP1. Biochem Pharmacol. 2001; 62(2):199-206. DOI: 10.1016/s0006-2952(01)00660-8. View

Anthonisen N, Connett J, Kiley J, Altose M, Bailey W, Buist A . Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA. 1994; 272(19):1497-505. View

Wielinga P, van der Heijden I, Reid G, Beijnen J, Wijnholds J, Borst P . Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells. J Biol Chem. 2003; 278(20):17664-71. DOI: 10.1074/jbc.M212723200. View

OConnell E . Review of the unique properties of budesonide. Clin Ther. 2003; 25 Suppl C:C42-60. DOI: 10.1016/s0149-2918(03)80305-3. View

10.

Gustafsson B, Persson C . Effect of different bronchodilators on airway smooth muscle responsiveness to contractile agents. Thorax. 1991; 46(5):360-5. PMC: 1020967. DOI: 10.1136/thx.46.5.360. View

11.

Bandi N, Kompella U . Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1). Eur J Pharmacol. 2002; 437(1-2):9-17. DOI: 10.1016/s0014-2999(02)01267-0. View

12.

Anderson G, Linden A, Rabe K . Why are long-acting beta-adrenoceptor agonists long-acting?. Eur Respir J. 1994; 7(3):569-78. DOI: 10.1183/09031936.94.07030569. View

13.

Calverley P, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H . Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J. 2003; 22(6):912-9. DOI: 10.1183/09031936.03.00027003. View

14.

Langmann T, Mauerer R, Zahn A, Moehle C, Probst M, Stremmel W . Real-time reverse transcription-PCR expression profiling of the complete human ATP-binding cassette transporter superfamily in various tissues. Clin Chem. 2003; 49(2):230-8. DOI: 10.1373/49.2.230. View

15.

Brechot J, Hurbain I, Fajac A, Daty N, Bernaudin J . Different pattern of MRP localization in ciliated and basal cells from human bronchial epithelium. J Histochem Cytochem. 1998; 46(4):513-7. DOI: 10.1177/002215549804600411. View

16.

Akan I, Akan S, Akca H, Savas B, Ozben T . Multidrug resistance-associated protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine sulfoximine. Cancer Cell Int. 2005; 5(1):22. PMC: 1183228. DOI: 10.1186/1475-2867-5-22. View

17.

Evers R, de Haas M, Sparidans R, Beijnen J, Wielinga P, Lankelma J . Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000; 83(3):375-83. PMC: 2374564. DOI: 10.1054/bjoc.2000.1262. View

18.

Borchard G, Cassara M, Roemele P, Florea B, Junginger H . Transport and local metabolism of budesonide and fluticasone propionate in a human bronchial epithelial cell line (Calu-3). J Pharm Sci. 2002; 91(6):1561-7. DOI: 10.1002/jps.10151. View

19.

Decramer M, Rutten-van Molken M, Dekhuijzen P, Troosters T, van Herwaarden C, Pellegrino R . Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005; 365(9470):1552-60. DOI: 10.1016/S0140-6736(05)66456-2. View

20.

Leslie E, Ito K, Upadhyaya P, Hecht S, Deeley R, Cole S . Transport of the beta -O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). Requirement for glutathione or a non-sulfur-containing analog. J Biol Chem. 2001; 276(30):27846-54. DOI: 10.1074/jbc.M102453200. View