Azithromycin and Clarithromycin Inhibit Lipopolysaccharide-Induced Murine Pulmonary Neutrophilia Mainly through Effects on Macrophage-Derived Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-1β
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作者:
Bosnar, Martina
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Bosnar, Martina
[1
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Bosnjak, Berislav
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Bosnjak, Berislav
[1
]
Cuzic, Snjezana
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Cuzic, Snjezana
[1
]
Hrvacic, Boska
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Hrvacic, Boska
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]
Marjanovic, Nikola
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Marjanovic, Nikola
[1
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Glojnaric, Ines
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Glojnaric, Ines
[1
]
Culic, Ognjen
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Culic, Ognjen
[1
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Parnham, Michael J.
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Parnham, Michael J.
[1
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Haber, Vesna Erakovic
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GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, CroatiaGlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Haber, Vesna Erakovic
[1
]
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[1] GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia
Macrolide antibiotics possess immunomodulatory/anti-inflammatory properties. These properties are considered fundamental for the efficacy of macrolide antibiotics in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, the molecular mechanisms and cellular targets of anti-inflammatory/immunomodulatory macrolide activity are still not fully understood. To describe anti-inflammatory effects of macrolides in more detail and to identify potential biomarkers of their activity, we have investigated the influence of azithromycin and clarithromycin on the inflammatory cascade leading to neutrophil infiltration into lungs after intranasal lipopolysaccharide challenge in mice. Azithromycin and clarithromycin pretreatment reduced total cell and neutrophil numbers in bronchoalveolar lavage fluid and myeloperoxidase concentration in lung tissue. In addition, concentrations of several inflammatory mediators, including CCL2, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, and sE-selectin in lung homogenates were decreased after macrolide treatment. Inhibition of cytokine production observed in vivo was also corroborated in vitro in lipopolysaccharide-stimulated monocytes/macrophages, but not in an epithelial cell line. In summary, results presented in this article confirm that macrolides can suppress neutrophil-dominated pulmonary inflammation and suggest that the effect is mediated through inhibition of GMCSF and IL-1 beta production by alveolar macrophages. Besides GM-CSF and IL-1 beta, CCL2 and sE-selectin are also identified as potential biomarkers of macrolide anti-inflammatory activity in the lungs.
机构:
Manchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, EnglandManchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, England
Crosbie, P. A. J.
Woodhead, M. A.
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Manchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, EnglandManchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, England
机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Hodge, Sandra
Hodge, Greg
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Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Hodge, Greg
Jersmann, Hubertus
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Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Jersmann, Hubertus
Matthews, Geoffrey
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Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Matthews, Geoffrey
Ahern, Jessica
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Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Ahern, Jessica
Holmes, Mark
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机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Holmes, Mark
Reynolds, Paul N.
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Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
机构:
Manchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, EnglandManchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, England
Crosbie, P. A. J.
Woodhead, M. A.
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h-index: 0
机构:
Manchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, EnglandManchester Royal Infirm, Dept Resp Med, Manchester M13 9WH, Lancs, England
机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Hodge, Sandra
Hodge, Greg
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h-index: 0
机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Hodge, Greg
Jersmann, Hubertus
论文数: 0引用数: 0
h-index: 0
机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Jersmann, Hubertus
Matthews, Geoffrey
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机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Matthews, Geoffrey
Ahern, Jessica
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机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Ahern, Jessica
Holmes, Mark
论文数: 0引用数: 0
h-index: 0
机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Holmes, Mark
Reynolds, Paul N.
论文数: 0引用数: 0
h-index: 0
机构:
Royal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia
Univ Adelaide, Adelaide, SA, AustraliaRoyal Adelaide Hosp & Lung Res Lab, Dept Thorac Med, Hanson Inst, Adelaide, SA 5001, Australia