Azithromycin ameliorates OVA-induced airway remodeling in Balb/c mice via suppression of epithelial-to-mesenchymal transition
Azithromycin is a potent agent that prevents airway remodeling. In this study, we hypothesized that azithromycin (35 mg/kg orally) alleviated airway remodeling through suppression of epithelial-to-mesenchymal transition (EMT) via downregulation of transforming growth factor-beta 1 (TGF-β1)/receptor...
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Published in | International immunopharmacology Vol. 58; pp. 87 - 93 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
01.05.2018
Elsevier BV |
Subjects | |
Online Access | Get full text |
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Summary: | Azithromycin is a potent agent that prevents airway remodeling. In this study, we hypothesized that azithromycin (35 mg/kg orally) alleviated airway remodeling through suppression of epithelial-to-mesenchymal transition (EMT) via downregulation of transforming growth factor-beta 1 (TGF-β1)/receptor for activated C-kinase1 (RACK1)/snail in mice. An ovalbumin (OVA)-induced Balb/c mice airway allergic inflammatory model was used. Airway inflammation and remodeling were evaluated with hematoxylin and eosin (HE), periodic acid–Schiff (PAS), and Masson staining. E-cadherin and N-cadherin (molecular markers of EMT) were analyzed by immunofluorescence, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting; α-smooth muscle actin (α-SMA) was evaluated using immunohistochemistry (IHC), qRT-PCR, and western blotting; and expression of TGF-β1/RACK1/Snail in lungs was measured by qRT-PCR and western blotting. Our data showed that azithromycin significantly reduced inflammation score, peribronchial smooth muscle layer thickness, goblet cell metaplasia, and deposition of collage fibers (P < 0.05), and effectively suppressed airway EMT (upregulated E-cadherin level, and downregulated N-cadherin and α-SMA levels) compared with the OVA group (P < 0.05). Moreover, the increasing mRNA and protein expressions of TGF-β1 and RACK1 and mRNA level of Snail in lung tissue were all significantly decreased in azithromycin-treated mice (P < 0.05). Taken together, our results suggest that azithromycin has the greatest effects on reducing airway remodeling by inhibiting TGF-β1/RACK1/Snail signal and improving the EMT in airway epithelium.
•Airway EMT is the main mechanism in OVA induced airway allergic inflammatory model.•Azithromycin is an attractive treatment option for reducing airway EMT.•Azithromycin improved EMT via inhibition of TGF-β1/RACK1/Snail signal pathway. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1567-5769 1878-1705 |
DOI: | 10.1016/j.intimp.2018.03.016 |