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WNT/beta-catenin pathway modulates the TNF-alpha-induced inflammatory response in bronchial epithelial cells

Authors
Jang, JaewoongJung, YoonjuChae, SeyeonChung, Sang-InKim, Seok-MinYoon, Yoosik
Issue Date
Mar-2017
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
TNF-alpha; WNT; beta-catenin; Inflammation; Bronchial epithelial cell
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.484, no.2, pp 442 - 449
Pages
8
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume
484
Number
2
Start Page
442
End Page
449
URI
https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/4695
DOI
10.1016/j.bbrc.2017.01.156
ISSN
0006-291X
1090-2104
Abstract
In this study, TNF-alpha was found to activate the WNT/beta-catenin pathway in BEAS-2B human bronchial epithelial cells. Levels of phospho-LRP6, Dv1-2, and phospho-GSK-3 beta were elevated, while that of Axin was reduced by TNF-alpha treatment. Nuclear translocation of beta-catenin and the reporter activity of a beta-catenin-responsive promoter were increased by TNF-alpha treatment. Under the same experimental conditions, TNF-alpha activated the NF-kappa B signaling, which includes the phosphorylation and degradation of I kappa B and nuclear translocation and target DNA binding of NF-kappa B, and it was found that an inhibitor of NF-kappa B activation, JSH-23, inhibited TNF-alpha-induced Wnt signaling as well as NF-kappa B signaling. It was also found that recombinant Wnt proteins induced NF-kappa B nuclear translocations and its target DNA binding, suggesting that Wnt signaling and NF-kappa B signaling were inter-connected. TNF-alpha-induced modulations of I kappa B and NE-kappa B as well as pro-inflammatory cytokine expression were significantly suppressed by the transfection of beta-catenin siRNA compared to that of control siRNA. Transfection of a beta-catenin expression plasmid augmented the TNF-alpha-induced modulations of I kappa B and NF-kappa B as well as pro-inflammatory cytokine expression. These results clearly demonstrated that the WNT/beta-catenin pathway modulates the inflammatory response induced by TNF-alpha, suggesting that this pathway may be a useful target for the effective treatment of bronchial inflammation. (C) 2017 Published by Elsevier Inc.
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