Jaewoong Jang1, Yoonju Jung1, Seyeon Chae1, Taehyun Bae1, Seok-Min Kim2, Yae Jie Shim3, Sang-In Chung1, Yoosik Yoon1. 1. a Department of Microbiology , Chung-Ang University College of Medicine , Seoul , Republic of Korea. 2. b School of Mechanical Engineering , Chung-Ang University , Seoul , Republic of Korea. 3. c College of General Studies , Sangmyung University , Seoul , Republic of Korea.
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.
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.