Open AccessAzithromycin inhibits nuclear factor‐ κ B activation during lung inflammation: an in vivo imaging study
Author(s) -
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
Publication year - 2014
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.58
Subject(s) - proinflammatory cytokine , bronchoalveolar lavage , in vivo , luciferase , inflammation , bioluminescence imaging , lipopolysaccharide , nf κb , nfkb1 , lung , chemistry , medicine , transfection , pharmacology , immunology , biology , transcription factor , biochemistry , microbiology and biotechnology , gene
We studied in vivo the potential involvement of nuclear factor‐ κ B ( NF ‐ κ B) 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 ‐ κ B responsive element were used to assess in vivo NF ‐ κ B 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 ‐ κ B responsive element, with significant luciferase expression in resident cells such as endothelial and epithelial cells, as assessed by duoplex immunofluorescence staining. Activation of NF ‐ κ B and inflammatory cell lung infiltration linearly correlated when different doses of bortezomib were used to inhibit NF ‐ κ B 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 ‐ κ B nuclear translocation. The results obtained using a novel approach to monitor NF ‐ κ B activation, provided, for the first time, in vivo evidence that azithromycin treatment results in pulmonary anti‐inflammatory activity associated with the inhibition of NF ‐ κ B activation in the lung.