title: WNT/β-catenin pathway modulates the TNF-α-induced inflammatory response in bronchial epithelial cells.
abstract: 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.
authors.affiliation: Department of Microbiology, Chung-Ang University, College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Jaewoong
authors.initials: J
authors.lastname: Jang
authors.affiliation: Department of Microbiology, Chung-Ang University, College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Yoonju
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Microbiology, Chung-Ang University, College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Chae
authors.affiliation: Department of Microbiology, Chung-Ang University, College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Sang-In
authors.initials: SI
authors.lastname: Chung
authors.affiliation: School of Mechanical Engineering, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Seok-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Chung-Ang University, College of Medicine, Seoul 156-756, Republic of Korea. Electronic address: thanks@cau.ac.kr.
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Yoon
mesh_terms: D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Bronchial epithelial cell; Inflammation; TNF-α; WNT; β-catenin