Journal Article

Moxifloxacin inhibits cytokine-induced MAP kinase and NF-κB activation as well as nitric oxide synthesis in a human respiratory epithelial cell line

Sara Werber, Itamar Shalit, Ina Fabian, Guy Steuer, Taly Weiss and Hannah Blau

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 55, issue 3, pages 293-300
Published in print March 2005 | ISSN: 0305-7453
Published online March 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh525
Moxifloxacin inhibits cytokine-induced MAP kinase and NF-κB activation as well as nitric oxide synthesis in a human respiratory epithelial cell line

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Background: We previously demonstrated that the quinolone moxifloxacin prevents Candida albicans pneumonitis and epithelial nuclear factor κB (NF-κB) nuclear translocation in immunosuppressed mice.

Objectives: To explore the anti-inflammatory effects of moxifloxacin directly on a lung epithelial cell line.

Methods: We studied the effect of clinically relevant concentrations of moxifloxacin (2.5–10 mg/L) on cytokine-induced activation of nitric oxide (NO) secretion, inducible NO synthase (iNOS) expression and the activation of signal transduction pathways of inflammation, NF-κB and the mitogen-activated protein kinases [extracellular signal-regulated kinases (ERK1/2) and C-Jun N-terminal kinase (JNK)], in the A549 lung epithelial cell line.

Results: Stimulation with the cytokines interleukin-1β(IL-1β)/interferon-γ (IFN-γ) increased NO up to 3.3-fold and moxifloxacin inhibited this up to 68% (P < 0.05). Similarly, the increase in iNOS levels was inhibited in cells pre-treated with moxifloxacin by up to 62%. IL-1β stimulated a rapid increase in the activities of early intracellular signalling molecules, ERK1/2 and JNK. Moxifloxacin inhibited ERK1/2 by up to 100% and p-JNK activation by 100%. NF-κB, as measured by electrophoretic mobility shift assay, was inhibited up to 72% by moxifloxacin. Western-blot analysis revealed that IL-1β enhanced NF-κB p65 and p50 proteins by 1.7- and 3.6-fold, respectively, whereas moxifloxacin inhibited the proteins by up to 60%.

Conclusions: Moxifloxacin inhibits intracellular signalling, iNOS expression and NO secretion in a lung epithelial cell line. Future studies may uncover a primary site of quinolone immunomodulation, either upstream or at the cell membrane. Eventually, this quinolone might become an important therapy for inflammatory lung diseases.

Keywords: quinolone; immunomodulation; intracellular signalling pathways; lung inflammation; A549 cells

Journal Article.  5226 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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