Involvement of p120 in LPS-induced NF-kappaB activation and IL-8 production in human bronchial epithelial cells.
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-kappaB (NF-kappaB) nuclear translocation was promoted and NF-kappaB 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-kappaB 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-kappaB 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-kappaB signaling.
Wang
Manxiang
M
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Pulmonary Disease, Ministry of Health of China, No. 13 Hangkong Road, Wuhan, Hubei, PR China.
Li
Naping
N
Li
Jiansha
J
Ma
Yan
Y
Li
Dan
D
Qin
Lingzhi
L
Wang
Xi
X
Wu
Renliang
R
D021581:Active Transport, Cell Nucleus; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D021122:Protein Subunits; D020545:Respiratory Mucosa / Q000166:cytology; D015398:Signal Transduction; D020729:p120 GTPase Activating Protein / Q000378:metabolism*
D020672:I-kappa B Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D020729:p120 GTPase Activating Protein