Azithromycin inhibits macrophage interleukin-1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia

被引:45
作者
Bosnar, Martina [1 ]
Cuzic, Snjezana [1 ]
Bosnjak, Berislav [1 ]
Nujic, Krunoslav [1 ]
Ergovic, Gabrijela [1 ]
Marjanovic, Nikola [1 ]
Pasalic, Ivanka [1 ]
Hrvacic, Boska [1 ]
Polancec, Denis [1 ]
Glojnaric, Ines [1 ]
Haber, Vesna Erakovic [1 ]
机构
[1] GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
关键词
Activator protein-1; Azithromycin; Interleukin-1; beta; Lipopolysaccharide-induced pulmonary neutrophilia; NECROSIS-FACTOR-ALPHA; BRONCHOALVEOLAR LAVAGE FLUID; KAPPA-B ACTIVATION; DIFFUSE PANBRONCHIOLITIS; MACROLIDE ANTIBIOTICS; ANTIINFLAMMATORY ACTIVITY; IN-VITRO; EXPRESSION; CLARITHROMYCIN; TRANSCRIPTION;
D O I
10.1016/j.intimp.2010.12.010
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1 beta (IL-1 beta) 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-1 beta 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-kappa B) 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-1 beta 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. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:424 / 434
页数:11
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