Document Detail


Azithromycin inhibits macrophage interleukin-1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia.
MedLine Citation:
PMID:  21195124     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Macrolide antibiotics, including azithromycin, also possess anti-inflammatory properties. However, the molecular mechanism(s) of activity as well as the target cells for their action have not been unambiguously identified as yet. In this study, the effects of azithromycin on lipopolysaccharide (LPS)-induced pulmonary neutrophilia were investigated in mice. Using immunohistochemistry, mRNA and specific protein assays, we confirmed that azithromycin ameliorates LPS-induced pulmonary neutrophilia by inhibiting interleukin-1β (IL-1β) expression and production selectively in alveolar macrophages as well as in LPS-stimulated J774.2 macrophage-derived cells in vitro. Inhibition by azithromycin of neutrophilia and IL-1β was accompanied by prevention of nuclear expression of activator protein-1 (AP-1) in both alveolar macrophages and J774.2 cells. The macrolide did not alter nuclear factor kappa B (NF-κB) or extracellular signal-regulated kinase 1/2 (ERK1/2) expression, activation or localization in LPS-stimulated lungs or in J774.2 cells. In conclusion, we have shown that inhibition of LPS-induced pulmonary neutrophilia and IL-1β concentrations in lung tissue following azithromycin treatment is mediated through effects on alveolar macrophages. In addition, we have shown for the first time, in an in vivo model, that azithromycin inhibits AP-1 activation in alveolar macrophages, an action confirmed on J774.2 cells in vitro.
Authors:
Martina Bosnar; Snježana Čužić; Berislav Bošnjak; Krunoslav Nujić; Gabrijela Ergović; Nikola Marjanović; Ivanka Pašalić; Boška Hrvačić; Denis Polančec; Ines Glojnarić; Vesna Eraković Haber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-30
Journal Detail:
Title:  International immunopharmacology     Volume:  11     ISSN:  1878-1705     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-18     Completed Date:  2011-07-14     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  424-34     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
GlaxoSmithKline Research Centre Zagreb Limited, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. martina.bosnar@glpg.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Azithromycin / pharmacology*
Bronchoalveolar Lavage Fluid / cytology,  immunology
Cell Line
Enzyme-Linked Immunosorbent Assay
Extracellular Signal-Regulated MAP Kinases / immunology,  metabolism
Immunohistochemistry
Interleukin-1beta / biosynthesis*,  immunology
Lipopolysaccharides / toxicity
Lung / drug effects,  immunology*,  metabolism
Macrophages / drug effects,  immunology
Male
Mice
Mice, Inbred BALB C
NF-kappa B / immunology,  metabolism
Neutrophil Infiltration / drug effects*,  immunology
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor AP-1 / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Interleukin-1beta; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Transcription Factor AP-1; 0/lipopolysaccharide, Escherichia coli 0111 B4; 83905-01-5/Azithromycin; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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