XAV939, a Wnt/-catenin pathway modulator, has inhibitory effects on LPS-induced inflammatory response

Aim: In this study, we report the anti-inflammatory activity of XAV939, a modulator of the Wnt/-catenin pathway.Methods: WNT/-catenin pathway and NF-B signaling pathway were examined in LPS-stimulated human bronchial epithelial cells and effects of XAV939 on these pathways were analyzed. The effect of XAV939 was confirmed in human umbilical vein endothelial cells.Results: LPS-induced expressions of pro-inflammatory genes IL-6, IL-8, TNF-, IL-1, MCP-1, MMP-9, iNOS and COX-2 were significantly and dose-dependently suppressed by XAV939. LPS-induced NF-B signaling, such as IB phosphorylation and degradation as well as nuclear translocation of NF-B, was also suppressed by XAV939. Target DNA binding of NF-B was significantly and dose-dependently suppressed by XAV939 during LPS-induced inflammatory response. The suppressive effects of XAV939 on NF-B signaling, target DNA binding of NF-B and pro-inflammatory gene expression were all rescued by over expression of -catenin, which shows that the anti-inflammatory effect of XAV939 is mediated by the modulation of -catenin, a central component of the WNT/-catenin pathway.Conclusion: The findings of this study showed that XAV939 exerts anti-inflammatory effects through the modulation of the Wnt/-catenin pathway.