β-catenin mediates the inflammatory cytokine expression induced by the Der p 1 house dust mite allergen

Abstract

The modulations of -catenin were analyzed during the inflammatory response induced by the Der p 1 house dust mite allergen. Der p 1 induced the dose-dependent expression of inflammatory cytokines, including interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor- (TNF-) in THP-1 human monocytic cells. The mRNA expression levels of -catenin were not altered, however protein levels increased following Der p 1 treatment, demonstrating that -catenin was modulated by post-transcriptional processes. It was also revealed that nuclear -catenin levels were significantly increased while cytoplasmic -catenin levels were reduced, which demonstrated the nuclear translocation of -catenin by the Der p 1 allergen. Glycogen synthase kinase 3 (GSK3), a regulator of -catenin stability, was demonstrated to be phosphorylated following Der p 1 treatment. When -catenin was knocked down by the transfection of its small interfering RNA (siRNA), inflammatory cytokine expression as well as nuclear factor-B (NF-B) activity, which were induced by Der p 1 treatment, were all significantly reduced. The results demonstrated that Der p 1-induced inflammatory responses were mediated by beta-catenin.