β-catenin regulates NF-κB activity and inflammatory cytokine expression in bronchial epithelial cells treated with lipopolysaccharide

In the present study, we demonstrate that lipopolysaccharide (LPS) induces the expression of inflammatory cytokines, including interleukin (IL)-6, IL-8, IL-1 beta; tumor necrosis factor (TNF)-alpha 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)-kappa B. When the expression of beta-catenin was analyzed following treatment with LPS, the mRNA level was unaltered; however, the beta-catenin protein levels increased with a decrease in phosphorylation at the serine 33/37 residues. Nuclear beta-catenin protein levels also increased along with the reporter activity of a beta-catenin-responsive TOPFlash vector. To elucidate the regulatory role of beta-catenin in the LPS-induced inflammatory response of bronchial epithelial cells, beta-catenin production was knocked down using siRNA. Our results revealed that beta-catenin protein levels and TOPFlash vector reporter activity were reduced to basal levels by siRNA transfection. In this experimental condition, NF-kappa B activity, measured by enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility shift assay (EMSA) and an NF-kappa B responsive reporter assay, was reduced to basal levels. Similarly, LPS-induced inflammatory cytokine expression was reduced almost to basal levels following transfection with beta-catenin siRNA. These results demonstrate that beta-catenin positively regulates NF-kappa B activity, as well as the expression of inflammatory cytokines in the inflammatory response of LPS-treated bronchial epithelial cells.