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

摘要

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.