WNT/β-catenin pathway modulates the TNF-α-induced inflammatory response in bronchial epithelial cells
- Department of Microbiology, Chung-Ang University, College of Medicine, Seoul 156-756 (Korea, Republic of)
- School of Mechanical Engineering, Chung-Ang University, Seoul 156-756 (Korea, Republic of)
In this study, TNF-α was found to activate the WNT/β-catenin pathway in BEAS-2B human bronchial epithelial cells. Levels of phospho-LRP6, Dvl-2, and phospho-GSK-3β were elevated, while that of Axin was reduced by TNF-α treatment. Nuclear translocation of β-catenin and the reporter activity of a β-catenin-responsive promoter were increased by TNF-α treatment. Under the same experimental conditions, TNF-α activated the NF-κB signaling, which includes the phosphorylation and degradation of IκB and nuclear translocation and target DNA binding of NF-κB, and it was found that an inhibitor of NF-κB activation, JSH-23, inhibited TNF-α-induced Wnt signaling as well as NF-κB signaling. It was also found that recombinant Wnt proteins induced NF-κB nuclear translocations and its target DNA binding, suggesting that Wnt signaling and NF-κB signaling were inter-connected. TNF-α-induced modulations of IκB and NF-κB as well as pro-inflammatory cytokine expression were significantly suppressed by the transfection of β-catenin siRNA compared to that of control siRNA. Transfection of a β-catenin expression plasmid augmented the TNF-α-induced modulations of IκB and NF-κB as well as pro-inflammatory cytokine expression. These results clearly demonstrated that the WNT/β-catenin pathway modulates the inflammatory response induced by TNF-α, suggesting that this pathway may be a useful target for the effective treatment of bronchial inflammation. - Highlights: • TNF-α activated the WNT/β-catenin pathway in bronchial epithelial cells. • TNF-α-induced WNT/β-catenin pathway was inhibited by NF-κB inhibitor. • Wnt proteins induced nuclear translocation and target DNA binding of NF-κB. • TNF-α-induced NF-κB signaling was suppressed by β-catenin knock-down. • TNF-α-induced NF-κB signaling was augmented by ectopic β-catenin expression.
- OSTI ID:
- 22696896
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 484, Issue 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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