JAC Advance Access originally published online on January 19, 2005
Journal of Antimicrobial Chemotherapy 2005 55(3):293-300; doi:10.1093/jac/dkh525
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JAC vol.55 no.3 © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Moxifloxacin inhibits cytokine-induced MAP kinase and NF-
B activation as well as nitric oxide synthesis in a human respiratory epithelial cell line
1 Department of Cell Biology and Histology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv; 2 Schneider Children's Medical Centre of Israel and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv; 3 Paediatric Department, Assaf Harofeh Medical Centre and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
* Correspondence address. Pulmonary Unit and Graub Cystic Fibrosis Centre, Schneider Children's Medical Centre of Israel, 14 Kaplan Street, Petah Tikva, 49202, Israel. Tel: +972-3-9253654; Fax: +972-3-9253147; Email: hblau{at}post.tau.ac.il
Background: We previously demonstrated that the quinolone moxifloxacin prevents Candida albicans pneumonitis and epithelial nuclear factor 
B (NF-B) 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-B 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-1ß(IL-1ß)/interferon-
(IFN-) 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-1ß 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-B, as measured by electrophoretic mobility shift assay, was inhibited up to 72% by moxifloxacin. Western-blot analysis revealed that IL-1ß enhanced NF-B 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
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