P120-catenin (p120), a prototypic member of a subfamily of Armadillo repeat domain (Arm domain) proteins, not only participates in cell-cell adhesion, but also mediates inflammatory responses in the skin. In the present study, we demonstrated the effect of p120 on lipopolysaccharide (LPS)-induced inflammatory responses in human bronchial epithelial cells (BECs). We first confirmed that p120 expression was significantly reduced after LPS stimulation in BECs, the p65 subunit of nuclear factor-kappa B (NF-kappa B) nuclear translocation was promoted and NF-kappa B activity was rapidly induced. Moreover, the expression level of interleukin-8 (IL-8) increased after LPS treatment. Over-expression of p120 attenuated LPS-stimulated NF-kappa B reporter gene expression and IL-8 mRNA expression and protein synthesis. On the contrary, transfection with p120 small interfering RNA (siRNA) significantly elevated LPS-stimulated NF-kappa B transcriptional activity, p65 nuclear translocation and IL-8 expression. Collectively, these results indicate an anti-inflammatory effect of p120 in BECs, through its modulation of NF-kappa B signaling. (C) 2010 Elsevier Ireland Ltd. All rights reserved.