p120 modulates LPS-induced NF-κB activation partially through RhoA in bronchial epithelial cells

Biomed Res Int. 2014:2014:932340. doi: 10.1155/2014/932340. Epub 2014 Jun 3.

Abstract

p120-Catenin (p120) is an adherens junction protein recognized to regulate cell-cell adhesion. Emerging evidence indicates that p120 may also play an important role in inflammatory responses, and the regulatory mechanisms are still unknown. In the present study, we showed that p120 was associated with airway inflammation. p120 downregulation induced nuclear factor-κB (NF-κB) activation, accompanied with I κ B α degradation, p65 nuclear translocation, and increased expression of interleukin-8 (IL-8) in lipopolysaccharide (LPS)- treated C57BL mice and human bronchial epithelial cells (BECs). Moreover, we first found that p120 directly coprecipitated with RhoA in BECs. After LPS stimulation, although total RhoA and p120-bound RhoA were unchanged, RhoA activity was increased. Y27632, a ROCK inhibitor, could partially inhibit nuclear translocation of p65. Overexpression of p120 inactivated RhoA and NF-κB in BECs, whereas p120 loss significantly increased RhoA activity, p65 nuclear translocation, and IL-8 expression. Taken together, our study supports the regulatory role of p120 in airway inflammation and reveals that p120 may modulate NF-κB signaling partially through RhoA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchi / metabolism
  • Bronchi / pathology
  • Catenins / genetics*
  • Catenins / metabolism
  • Delta Catenin
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation / genetics
  • Humans
  • Inflammation / chemically induced
  • Inflammation / genetics*
  • Inflammation / pathology
  • Interleukin-8 / biosynthesis
  • Lipopolysaccharides / toxicity
  • NF-kappa B / biosynthesis*
  • NF-kappa B / genetics
  • Signal Transduction / genetics
  • rhoA GTP-Binding Protein / biosynthesis*
  • rhoA GTP-Binding Protein / genetics

Substances

  • Catenins
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • RHOA protein, human
  • rhoA GTP-Binding Protein
  • Delta Catenin
  • CTNND1 protein, human