C-EBPβ mediates in cigarette/IL-17A-induced bronchial epithelial-mesenchymal transition in COPD mice

Background Cigarettes smoking and IL-17A contribute to chronic obstructive pulmonary disease (COPD), and have synergistical effect on bronchial epithelial cell proliferation. CCAAT/enhancer-binding protein beta (C-EBP beta) could be induced by IL-17A and is up-regulated in COPD. We explored the effect of cigarettes and IL-17 on bronchial epithelial-mesenchymal transition (EMT) in COPD mice and potential mechanism involved with C-EBP beta in this study. Methods COPD model was established with mice by exposing to cigarettes. E-Cadherin, Vimentin, IL-17A and C-EBP beta distributions were detected in lung tissues. Primary bronchial epithelial cells were separated from health mice and cocultured with cigarette smoke extract (CSE) or/and IL-17A. E-Cadherin, Vimentin and IL-17 receptor (IL-17R) expressions in vitro were assessed. When C-EBP beta were silenced by siRNA in cells, E-Cadherin, Vimentin and C-EBP beta expressions were detected. Results E-Cadherin distribution was less and Vimentin distribution was more in bronchus of COPD mice than controls. IL-17A and C-EBP beta expressions were higher in lung tissues of COPD mice than controls. In vitro, C-EBP beta protein expression was highest in CSE + IL-17A group, followed by CSE and IL-17A groups. E-cadherin expression in vitro was lowest and Vimentin expression was highest in CSE + IL-17A group, followed by CSE or IL-17A group. Those could be inhibited by C-EBP beta silenced. Conclusions C-EBP beta mediates in cigarette/IL-17A-induced bronchial EMT in COPD mice. Our findings contribute to a better understanding on the progress from COPD to lung cancers, which will provide novel avenues in preventing tumorigenesis of airway in the context of cigarette smoking.

Automated summary

The study reveals that C-EBP beta mediates cigarette/IL-17A-induced bronchial EMT in COPD mice. These findings contribute to a better understanding of the progression from COPD to lung cancers, providing novel avenues for preventing tumorigenesis of the airway in the context of cigarette smoking.