Azithromycin alters macrophage phenotype
Azithromycin alters macrophage phenotype
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DOI：
10.1093/jac/dkn007
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发表时间：
2008-03-01
影响因子：
5.2
通讯作者：
Feola, David J.
中科院分区：
文献类型：
--
作者：
Murphy, Brian S.;Sundareshan, Vidya;Feola, David J.
目的：探讨阿奇霉素对体外巨噬细胞表型的影响。利用小鼠巨噬细胞系（J774），我们研究了阿奇霉素对定义经典巨噬细胞激活（M1）和替代巨噬细胞激活（M2）特性的影响。方法：在阿奇霉素作用下培养J774细胞，用经典激活[干扰素γ (IFN γ)]和替代激活[白细胞介素(IL)-4和IL-13]细胞因子及脂多糖（LPS）刺激J774细胞。分析巨噬细胞炎性细胞因子产生、表面受体表达、诱导型一氧化氮合酶（iNOS）蛋白表达和精氨酸酶活性。结果：阿奇霉素改变了巨噬细胞的整体表型。阿奇霉素处理的J774巨噬细胞显示出促炎细胞因子IL-12和IL-6的产生显著减少，抗炎细胞因子IL-10的产生增加，IL-12 / IL-10的比值降低了60%。M2表型的受体（甘露糖受体和CD23）表达增加，M1细胞中典型上调的受体（CCR7）表达被抑制。阿奇霉素的存在使IFN γ和LPS刺激的细胞中精氨酸酶（M2效应分子）活性增加10倍，并使iNOS蛋白（M1效应分子）浓度降低。结论：这些数据提供了证据，证明阿奇霉素在巨噬细胞水平上影响炎症过程，并使巨噬细胞极化向交替激活表型转变。最近定义的M2表型已被描述为肺部炎症和纤维化是临床结果的主要决定因素，但抗生素改变巨噬细胞表型的概念尚未得到严格评估。
Objectives: To investigate the in vitro effects of azithromycin on macrophage phenotype. Utilizing a mouse macrophage cell line (J774), we examined the effect of azithromycin on the properties that define classical macrophage activation (M1) and alternative macrophage activation (M2).Methods: J774 cells were cultured in the presence of azithromycin and stimulated with classical activation [interferon-gamma (IFN gamma)] and alternative activation [interleukin (IL)-4 and IL-13] cytokines along with lipopolysaccharide (LPS). Macrophages were analysed for inflammatory cytokine production, surface receptor expression, inducible nitric oxide synthase (iNOS) protein expression and arginase activity.Results: Azithromycin altered the overall macrophage phenotype. Azithromycin-treated J774 macrophages demonstrated a significantly reduced production of the pro-inflammatory cytokines IL-12 and IL-6, increased production of the anti-inflammatory cytokine IL-10 and decreased the ratio of IL-12 to IL-10 by 60%. Receptor expression indicative of the M2 phenotype (mannose receptor and CD23) was increased, and receptor expression typically up-regulated in M1 cells (CCR7) was inhibited. The presence of azithromycin increased arginase (M2 effector molecule) activity 10-fold in cells stimulated with IFN gamma and LPS, and iNOS protein (M1 effector molecule) concentrations were attenuated by the drug.Conclusions: These data provide evidence that azithromycin affects the inflammatory process at the level of the macrophage and shifts macrophage polarization towards the alternatively activated phenotype. This recently defined M2 phenotype has been described in conditions in which pulmonary inflammation and fibrosis are major determinants of clinical outcome, but the concept of antibiotics altering macrophage phenotype has not yet been critically evaluated.