Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis.
Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis.
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DOI：
10.1016/j.jcf.2013.08.007
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Feola DJ
中科院分区：
文献类型：
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作者：
Cory TJ;Birket SE;Murphy BS;Hayes D Jr;Anstead MI;Kanga JF;Kuhn RJ;Bush HM;Feola DJ
阿奇霉素治疗可改善CF患者的临床参数，并将巨噬细胞活化从促炎（M1）表型改变为促纤维化、交替活化（M2）表型。接受阿奇霉素治疗的患者细胞的转录谱尚不清楚。从CF患者采集的痰液样本中评估与巨噬细胞极化、炎症和组织重塑相关的基因表达。比较转录谱和临床特征，包括阿奇霉素治疗。在接受阿奇霉素治疗的受试者中，NOS 2和TNFα的表达降低，而M2相关基因的表达不受影响。主成分分析显示，在选定的受试者组中，基因表达谱与M1-（MMP 9，NOS 2和TLR 4）或M2-极化（CCL 18，纤连蛋白和MR 1）一致。这些表达特征与临床特征无显著相关性。在接受AZM治疗的受试者中，促炎基因表达较低。基因分层的M1-或M2-极化的特征组件，表明整体极化状态是不同的患者群体。
Azithromycin treatment improves clinical parameters in patients with CF, and alters macrophage activation from a pro-inflammatory (M1) phenotype to a pro-fibrotic, alternatively activated (M2) phenotype. The transcriptional profile of cells from patients receiving azithromycin is unknown. Gene expression in association with macrophage polarization, inflammation, and tissue remodeling was assessed from sputum samples collected from patients with CF. Transcriptional profiles and clinical characteristics, including azithromycin therapy, were compared. Expression of NOS2 and TNFα was decreased in subjects receiving azithromycin, whereas expression of M2-associated genes was unaffected. Principal component analysis revealed gene expression profiles consistent with M1-(MMP9, NOS2, and TLR4) or M2-polarization (CCL18, fibronectin, and MR1) in select subject groups. These expression signatures did not significantly correlate with clinical characteristics. Pro-inflammatory gene expression was low in subjects receiving AZM. Genes stratified to components characteristic of M1- or M2-polarization, suggesting overall polarization status is distinct among patient groups.