| Modulation of the expression of ABC transporters in murine (J774) macrophages exposed to large concentrations of the fluoroquinolone antibiotic moxifloxacin. | |
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MedLine Citation:
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PMID: 21946100 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Long-term exposure to pharmacological agents can select for cells that overexpress efflux transporters. We previously showed that mouse J774 macrophages cultivated for a prolonged period of time with toxic concentrations of the fluoroquinolone ciprofloxacin overexpress the efflux transporter Mrp4 and display a reduced accumulation of this antibiotic, but no change in the accumulation of moxifloxacin, a closely related molecule (Antimicrob. Agents Chemother. [2006] 50, 1689-1695 and [2009], 2410-2416). Because of this striking difference between the two fluoroquinolones, we have now examined the modifications in the expression of ABC efflux transporters induced by the prolonged exposure of J774 macrophages to high concentrations of moxifloxacin. The resulting cell line showed (i) no difference in the accumulation of moxifloxacin but an increased accumulation and decreased efflux of ciprofloxacin; (ii) an overexpression of the multidrug transporters Abcb1a (P-gp), Abcc2 (Mrp2) and Abcg2 (Bcrp1), and a decreased expression of Abcc4 (Mrp4). While P-gp and Bcrp1 were functional, they did not modify the cellular accumulation of fluoroquinolones. The data show that exposing cells to high concentrations of a drug that is not affected by active efflux can trigger a pleiotropic response leading to a modulation in the expression of several transporters. These changes, however, are not sufficient to protect cells against the toxicity that fluoroquinolones may exert at large concentrations. They could also cause unanticipated drug interactions in vivo should the drug exposure grossly exceed what is anticipated from its current registered use. |
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Authors:
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Coralie M Vallet; Béatrice Marquez; Naïma Nhiri; Ahalieyah Anantharajah; Marie-Paule Mingeot-Leclercq; Paul M Tulkens; Jean-Yves Lallemand; Eric Jacquet; Françoise Van Bambeke |
Publication Detail:
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Type: - Date: 2011-9-17 |
Journal Detail:
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Title: Toxicology Volume: - ISSN: 1879-3185 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ireland Ltd. |
Affiliation:
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Université catholique de Louvain, Louvain Drug Research Institute, Pharmacologie cellulaire et moléculaire, B-1200 Brussels, Belgium. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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