Regional Differences in Susceptibiity of Bronchial Epithelium to Mesenchymal Transition and Inhibition by the Macrolide Antibiotic Azithromycin

Banerjee, Balarka, Musk, Michael, Sutanto, Erika N., Yerkovich, Stephanie T., Hopkins, Peter, Knight, Darryl A., Lindsey-Temple, Suzanna, Stick, Stephen M., Kicic, Anthony and Chambers, Daniel C. (2012) Regional Differences in Susceptibiity of Bronchial Epithelium to Mesenchymal Transition and Inhibition by the Macrolide Antibiotic Azithromycin. PLoS One, 7 12: e52309.1-e52309.12. doi:10.1371/journal.pone.0052309


Author Banerjee, Balarka
Musk, Michael
Sutanto, Erika N.
Yerkovich, Stephanie T.
Hopkins, Peter
Knight, Darryl A.
Lindsey-Temple, Suzanna
Stick, Stephen M.
Kicic, Anthony
Chambers, Daniel C.
Title Regional Differences in Susceptibiity of Bronchial Epithelium to Mesenchymal Transition and Inhibition by the Macrolide Antibiotic Azithromycin
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-12
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.pone.0052309
Open Access Status DOI
Volume 7
Issue 12
Start page e52309.1
End page e52309.12
Total pages 12
Place of publication San Francisco, CA., United States
Publisher Public Library of Science
Collection year 2013
Language eng
Formatted abstract
Objective: Dysregulated repair following epithelial injury is a key forerunner of disease in many organs, and the acquisition of a mesenchymal phenotype by the injured epithelial cells (epithelial to mesenchymal transition, EMT) may serve as a source of fibrosis. The macrolide antibiotic azithromycin and the DNA synthesis inhibitor mycophenolate are in clinical use but their mechanism of action remains unknown in post-transplant bronchiolitis obliterans syndrome (BOS). Here we determined if regional variation in the EMT response to TGFβ1 underlies the bronchiolocentric fibrosis leading to BOS and whether EMT could be inhibited by azithromycin or mycophenolate.

Methods/Results:
We found that small and large airway epithelial cells from stable lung transplant patients underwent EMT when stimulated with TGFβ1, however mesenchymal protein expression was higher and loss of epithelial protein expression more complete in small airway epithelial cells. This regional difference was not mediated by changes in expression of the TGFβRII or Smad3 activation. Azithromycin potentially inhibited EMT in both small and large airway epithelial cells by inhibiting Smad3 expression, but not activation.

Conclusion: Collectively, these observations provide a biologic basis for a previously unexplained but widely observed clinical phenomena, and a platform for the development of new approaches to fibrotic diseases.
Keyword Bronchiolitis obliterans syndrome
Lung Transplant Recipients
Growth factor beta
Renal Allograft Recipients
Mycophenolate Mofetil
Pseudomonas aeruginosa
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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