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Journal of Inflammation

, 7:56

First Online: 23 November 2010Received: 24 May 2010Accepted: 23 November 2010

Abstract

BackgroundLow-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. Since there is growing evidence that macrolide antibiotic-resistant bacteria-s spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin CAM and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts NPFs through the choice of nitric oxide NO, which is one of important effector molecule in the development of airway inflammatory disease in vitro.

MethodsNPFs 5 × 10 cells-ml were stimulated with 1.0 μg-ml lipopolysaccharide LPS in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-κB activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively.

ResultsThe addition of CAM > 0.4 μg-ml and M-4 > 0.04 μg-ml could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-κB activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 μg-ml of the agent was added to cell cultures.

ConclusionThe present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-9255-7-56 contains supplementary material, which is available to authorized users.

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Autor: Ayako Furuya - Kazuhito Asano - Naruo Shoji - Kojiro Hirano - Taisuke Hamasaki - Harumi Suzaki

Fuente: https://link.springer.com/







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