| Azithromycin inhibits macrophage interleukin-1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia. | |
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MedLine Citation:
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PMID: 21195124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-12-30 |
Journal Detail:
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Title: International immunopharmacology Volume: 11 ISSN: 1878-1705 ISO Abbreviation: Int. Immunopharmacol. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-18 Completed Date: 2011-07-14 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 100965259 Medline TA: Int Immunopharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 424-34 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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GlaxoSmithKline Research Centre Zagreb Limited, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. martina.bosnar@glpg.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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