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Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study

We studied in vivo the potential involvement of nuclear factor-κB (NF-κB) pathway in the molecular mechanism of the anti-inflammatory and immunomodulatory activity of azithromycin in the lung. Mice transiently transfected with the luciferase gene under the control of a NF-κB responsive element were...

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Autores principales: Stellari, Fabio F, Sala, Angelo, Donofrio, Gaetano, Ruscitti, Francesca, Caruso, Paola, Topini, Thomas M, Francis, Kevin P, Li, Xiaojian, Carnini, Chiara, Civelli, Maurizio, Villetti, Gino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186419/
https://www.ncbi.nlm.nih.gov/pubmed/25505605
http://dx.doi.org/10.1002/prp2.58
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author Stellari, Fabio F
Sala, Angelo
Donofrio, Gaetano
Ruscitti, Francesca
Caruso, Paola
Topini, Thomas M
Francis, Kevin P
Li, Xiaojian
Carnini, Chiara
Civelli, Maurizio
Villetti, Gino
author_facet Stellari, Fabio F
Sala, Angelo
Donofrio, Gaetano
Ruscitti, Francesca
Caruso, Paola
Topini, Thomas M
Francis, Kevin P
Li, Xiaojian
Carnini, Chiara
Civelli, Maurizio
Villetti, Gino
author_sort Stellari, Fabio F
collection PubMed
description We studied in vivo the potential involvement of nuclear factor-κB (NF-κB) pathway in the molecular mechanism of the anti-inflammatory and immunomodulatory activity of azithromycin in the lung. Mice transiently transfected with the luciferase gene under the control of a NF-κB responsive element were used to assess in vivo NF-κB activation by bioluminescence imaging. Bioluminescence as well as inflammatory cells and concentrations of proinflammatory cytokines in bronchoalveolar lavage fluids, were monitored in an acute model of pulmonary inflammation resulting from intratracheal instillation of lipopolysaccharide. Lipopolysaccharide (LPS) instillation induced a marked increase in lung bioluminescence in mice transiently transfected with the luciferase gene under the control of an NF-κB responsive element, with significant luciferase expression in resident cells such as endothelial and epithelial cells, as assessed by duoplex immunofluorescence staining. Activation of NF-κB and inflammatory cell lung infiltration linearly correlated when different doses of bortezomib were used to inhibit NF-κB activation. Pretreatment with azithromycin significantly decreased lung bioluminescence and airways cell infiltration induced by LPS, also reducing proinflammatory cytokines concentrations in bronchoalveolar lavages and inhibiting NF-κB nuclear translocation. The results obtained using a novel approach to monitor NF-κB activation, provided, for the first time, in vivo evidence that azithromycin treatment results in pulmonary anti-inflammatory activity associated with the inhibition of NF-κB activation in the lung.
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spelling pubmed-41864192014-12-03 Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study Stellari, Fabio F Sala, Angelo Donofrio, Gaetano Ruscitti, Francesca Caruso, Paola Topini, Thomas M Francis, Kevin P Li, Xiaojian Carnini, Chiara Civelli, Maurizio Villetti, Gino Pharmacol Res Perspect Original Articles We studied in vivo the potential involvement of nuclear factor-κB (NF-κB) pathway in the molecular mechanism of the anti-inflammatory and immunomodulatory activity of azithromycin in the lung. Mice transiently transfected with the luciferase gene under the control of a NF-κB responsive element were used to assess in vivo NF-κB activation by bioluminescence imaging. Bioluminescence as well as inflammatory cells and concentrations of proinflammatory cytokines in bronchoalveolar lavage fluids, were monitored in an acute model of pulmonary inflammation resulting from intratracheal instillation of lipopolysaccharide. Lipopolysaccharide (LPS) instillation induced a marked increase in lung bioluminescence in mice transiently transfected with the luciferase gene under the control of an NF-κB responsive element, with significant luciferase expression in resident cells such as endothelial and epithelial cells, as assessed by duoplex immunofluorescence staining. Activation of NF-κB and inflammatory cell lung infiltration linearly correlated when different doses of bortezomib were used to inhibit NF-κB activation. Pretreatment with azithromycin significantly decreased lung bioluminescence and airways cell infiltration induced by LPS, also reducing proinflammatory cytokines concentrations in bronchoalveolar lavages and inhibiting NF-κB nuclear translocation. The results obtained using a novel approach to monitor NF-κB activation, provided, for the first time, in vivo evidence that azithromycin treatment results in pulmonary anti-inflammatory activity associated with the inhibition of NF-κB activation in the lung. Blackwell Publishing Ltd 2014-10 2014-07-02 /pmc/articles/PMC4186419/ /pubmed/25505605 http://dx.doi.org/10.1002/prp2.58 Text en © 2014 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Stellari, Fabio F
Sala, Angelo
Donofrio, Gaetano
Ruscitti, Francesca
Caruso, Paola
Topini, Thomas M
Francis, Kevin P
Li, Xiaojian
Carnini, Chiara
Civelli, Maurizio
Villetti, Gino
Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study
title Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study
title_full Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study
title_fullStr Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study
title_full_unstemmed Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study
title_short Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study
title_sort azithromycin inhibits nuclear factor-κb activation during lung inflammation: an in vivo imaging study
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186419/
https://www.ncbi.nlm.nih.gov/pubmed/25505605
http://dx.doi.org/10.1002/prp2.58
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