Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis

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• 作者：Theodore J. Cory ; Susan E. Birket ; Brian S. Murphy ; Don Hayes Jr. ; Michael I. Anstead ; Jamshed F. Kanga ; Robert J. Kuhn ; Heather M. Bush ; David J. Feola
• 关键词：Macrophage phenotype ; Cystic fibrosis ; Azithromycin
• 刊名：Journal of Cystic Fibrosis
• 出版年：March, 2014
• 年：2014
• 卷：13
• 期：2
• 页码：164-171
• 全文大小：732 K

文摘

Background

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.

Methods

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.

Results

Expression of NOS2 and TNF伪 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.

Conclusions

Pro-inflammatory gene expression was low in subjects receiving AZM. Genes were stratified into groupings characteristic of M1- or M2-polarization, suggesting that overall polarization status is distinct among patient groups.