Moxifloxacin inhibits cytokine-induced MAP kinase and NF-kappaB activation as well as nitric oxide synthesis in a human respiratory epithelial cell line.
BACKGROUND: We previously demonstrated that the quinolone moxifloxacin prevents Candida albicans pneumonitis and epithelial nuclear factor kappaB (NF-kappaB) 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-kappaB 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-1beta(IL-1beta)/interferon-gamma ( IFN-gamma) 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-1beta 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-kappaB, as measured by electrophoretic mobility shift assay, was inhibited up to 72% by moxifloxacin. Western-blot analysis revealed that IL-1beta enhanced NF-kappaB 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.[1]References
- Moxifloxacin inhibits cytokine-induced MAP kinase and NF-kappaB activation as well as nitric oxide synthesis in a human respiratory epithelial cell line. Werber, S., Shalit, I., Fabian, I., Steuer, G., Weiss, T., Blau, H. J. Antimicrob. Chemother. (2005) [Pubmed]
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