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

Abstract

Aim: In this study, we report the anti-inflammatory activity of XAV939, a modulator of the Wnt/β-catenin pathway.

Methods: WNT/β-catenin pathway and NF-κB 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-α, IL-1β, MCP-1, MMP-9, iNOS and COX-2 were significantly and dose-dependently suppressed by XAV939. LPS-induced NF-κB signaling, such as IκB phosphorylation and degradation as well as nuclear translocation of NF-κB, was also suppressed by XAV939. Target DNA binding of NF-κB was significantly and dose-dependently suppressed by XAV939 during LPS-induced inflammatory response. The suppressive effects of XAV939 on NF-κB signaling, target DNA binding of NF-κB and pro-inflammatory gene expression were all rescued by over expression of β-catenin, which shows that the anti-inflammatory effect of XAV939 is mediated by the modulation of β-catenin, a central component of the WNT/β-catenin pathway.

Conclusion: The findings of this study showed that XAV939 exerts anti-inflammatory effects through the modulation of the Wnt/β-catenin pathway.

Keywords:

• XAV939
• Wnt/β-catenin pathway
• lipopolysaccharide
• inflammation; NF-κB

Disclosure statement

No potential conflict of interests was reported by the author(s).

Additional information

Funding

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea [NRF-2017R1D1A1B03029033], and by the Chung-Ang University Research Scholarship Grant in 2017 (Seyeon Chae).