Modulation of the expression of ABC transporters in murine (J774) macrophages exposed to large concentrations of the fluoroquinolone antibiotic moxifloxacin.

نویسندگان

  • Coralie M Vallet
  • Béatrice Marquez
  • Naïma Nhiri
  • Ahalieyah Anantharajah
  • Marie-Paule Mingeot-Leclercq
  • Paul M Tulkens
  • Jean-Yves Lallemand
  • Eric Jacquet
  • Françoise Van Bambeke
چکیده

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] 53, 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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Cooperation between prokaryotic (Lde) and eukaryotic (MRP) efflux transporters in J774 macrophages infected with Listeria monocytogenes: studies with ciprofloxacin and moxifloxacin.

Antibiotic efflux is observed in both eukaryotic and prokaryotic cells, modulating accumulation and resistance. The present study examines whether eukaryotic and prokaryotic fluoroquinolone transporters can cooperate in the context of an intracellular infection. We have used (i) J774 macrophages (comparing a ciprofloxacin-resistant cell line overexpressing an MRP-like transporter with wild-type...

متن کامل

STAT3 as a Key Factor in Tumor Microenvironment and Cancer Stem Cell

Background Recent studies revealed that tumor-associated macrophages (TAMs) play a decisive role in the regulation of tumor progression by manipulating tumor oncogenesis, angiogenesis and immune functions within tumor microenvironments. Signal transducer and activator of transcription 3 (STAT3), which is a point of convergence for numerous oncogenic signalling pathways, is constitutively activ...

متن کامل

بررسی حداقل غلظت مهاری رشد سیپروفلوکساسین در ترکیب با مشتقات هگزاهیدروکویینولین علیه استافیلوکوکوس اورئوس

Background: Staphylococcus aureus is the most common pathogen responsible for skin and soft tissue infections worldwide. Methicillin-resistant S. aureus is a major cause of both nosocomial and community acquired infections. The emergence of antimicrobial-resistant S. aureus is of global concern. Fluoroquinolone antimicrobials including ciprofloxacin, levofloxacin, and moxifloxacin are used to t...

متن کامل

اثر عصاره سیر بر بیان ژن‌های iNOSو IFNγ در رده سلولی J774 آلوده به لیشمانیا ماژور

  Background and Objectives : The protozoa of leishmania lead to cutaneus and visceral leishmaniasis. Activation macrophages phagocyte parasites and this mechanism can be done with production of active radicals oxygen and nitric oxide, That is done through immunomodulator , as a basic process for production of the new drug. In this study, the effect of garlic extract as an immunomodulator on J7...

متن کامل

Changes in the expression of MDR transporters in J774 mouse macrophages selected by chronic exposure to ciprofloxacin (CIP) or moxifloxacin (MXF), two fluoroquinolone antibiotics

C. Vallet, B. Marquez, N. Nhiri*, E. Jacquet*, M-P. Mingeot-Leclercq, P.M. Tulkens, F. Van Bambeke Unité de pharmacologie cellulaire et moléculaire, Université catholique de Louvain, Brussels, Belgium *Institut de chimie des substances naturelles, CNRS, Gif sur Yvette, France Mailing address : P.M. Tulkens, Pharmacologie cellulaire et moléculaire, UCL Bat. Van Helmont, 7370 Av. E. Mounier,1200 ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Toxicology

دوره 290 2-3  شماره 

صفحات  -

تاریخ انتشار 2011