WNT/β-catenin pathway modulates the TNF-α-induced inflammatory response in bronchial epithelial cells

Journal Article · Sat Mar 04 04:00:00 EST 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.01.156· OSTI ID:22696896

Jang, Jaewoong; Jung, Yoonju; Chae, Seyeon; Chung, Sang-In ^[1]; Kim, Seok-Min ^[2]; Yoon, Yoosik ^[1]

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1. Department of Microbiology, Chung-Ang University, College of Medicine, Seoul 156-756 (Korea, Republic of)
2. 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, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 484; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
INFLAMMATION
INHIBITION
MODULATION
SIGNALS
TRANSLOCATION