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

J Cyst Fibros. 2014 Mar;13(2):164-71. doi: 10.1016/j.jcf.2013.08.007. Epub 2013 Sep 7.

Abstract

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 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.

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.

Keywords: Azithromycin; Cystic fibrosis; Macrophage phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Azithromycin* / administration & dosage
  • Azithromycin* / adverse effects
  • Child
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / metabolism
  • Cystic Fibrosis* / physiopathology
  • Female
  • Gene Expression / drug effects*
  • Gene Expression Profiling
  • Genome-Wide Association Study
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Inflammation* / physiopathology
  • Macrophage Activation / drug effects
  • Macrophages, Alveolar* / drug effects
  • Macrophages, Alveolar* / physiology
  • Male
  • Phenotype
  • Receptors, Immunologic / metabolism
  • Respiratory Function Tests

Substances

  • Anti-Bacterial Agents
  • Inflammation Mediators
  • Receptors, Immunologic
  • Azithromycin