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Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis
Affiliation:1. Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone, Lexington, KY 40536, United States;2. Department of Pharmacy Practice, University of Nebraska College of Pharmacy, 986000 Nebraska Medical Center, Omaha, NE 68198, United States;3. Department of Medicine, University of Alabama at Birmingham, 1918 University Blvd., Birmingham, AL 35294, United States;4. Department of Internal Medicine, University of Kentucky College of Medicine, 138 Leader Avenue, Lexington, KY 40506, United States;5. Section of Pulmonary Medicine, Department of Pediatrics, The Ohio State University, Nationwide Children''s Hospital, 700 Children''s Dr., Columbus, OH 43205, United States;6. Department of Pediatrics, University of Kentucky, 138 Leader Avenue, Lexington, KY 40506, United States;7. Department of Biostatistics, University of Kentucky College of Medicine, 725 Rose Street, Lexington, KY 40536, United States
Abstract:BackgroundAzithromycin 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.MethodsGene 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.ResultsExpression 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.ConclusionsPro-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.
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