TY - JOUR
T1 - Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis
AU - Cory, Theodore J.
AU - Birket, Susan E.
AU - Murphy, Brian S.
AU - Hayes, Don
AU - Anstead, Michael I.
AU - Kanga, Jamshed F.
AU - Kuhn, Robert J.
AU - Bush, Heather M.
AU - Feola, David J.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Azithromycin
KW - Cystic fibrosis
KW - Macrophage phenotype
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U2 - 10.1016/j.jcf.2013.08.007
DO - 10.1016/j.jcf.2013.08.007
M3 - Article
C2 - 24018177
AN - SCOPUS:84895069717
SN - 1569-1993
VL - 13
SP - 164
EP - 171
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
IS - 2
ER -