title: Β-catenin regulates NF-κB activity and inflammatory cytokine expression in bronchial epithelial cells treated with lipopolysaccharide.
abstract: In the present study, we demonstrate that lipopolysaccharide (LPS) induces the expression of inflammatory cytokines, including interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in BEAS-2B human bronchial epithelial cells in a dose- and time-dependent manner. This increase was accompanied by an increased activity of nuclear factor (NF)‑κB. When the expression of β-catenin was analyzed following treatment with LPS, the mRNA level was unaltered; however, the β-catenin protein levels increased with a decrease in phosphorylation at the serine 33/37 residues. Nuclear β-catenin protein levels also increased along with the reporter activity of a β-catenin-responsive TOPFlash vector. To elucidate the regulatory role of β-catenin in the LPS-induced inflammatory response of bronchial epithelial cells, β-catenin production was knocked down using siRNA. Our results revealed that β-catenin protein levels and TOPFlash vector reporter activity were reduced to basal levels by siRNA transfection. In this experimental condition, NF-κB activity, measured by enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility shift assay (EMSA) and an NF-κB responsive reporter assay, was reduced to basal levels. Similarly, LPS-induced inflammatory cytokine expression was reduced almost to basal levels following transfection with β-catenin siRNA. These results demonstrate that β-catenin positively regulates NF-κB activity, as well as the expression of inflammatory cytokines in the inflammatory response of LPS-treated bronchial epithelial cells.
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: Jong-Hyeok
authors.initials: JH
authors.lastname: Ha
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: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Yoon
mesh_terms: D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051176:beta Catenin