XAV939, a Wnt/β-catenin pathway modulator, has inhibitory effects on LPS-induced inflammatory response
- Authors
- Jang, Jaewoong; Jung, Yoonju; Chae, Seyeon; Bae, Taehyun; Kim, Seok-Min; Shim, Yae Jie; Chung, Sang-In; Yoon, Yoosik
- Issue Date
- May-2019
- Publisher
- Taylor and Francis Ltd
- Keywords
- inflammation; NF-κB; lipopolysaccharide; Wnt/β-catenin pathway; XAV939
- Citation
- Immunopharmacology and Immunotoxicology, v.41, no.3, pp 394 - 402
- Pages
- 9
- Journal Title
- Immunopharmacology and Immunotoxicology
- Volume
- 41
- Number
- 3
- Start Page
- 394
- End Page
- 402
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/3355
- DOI
- 10.1080/08923973.2018.1536984
- ISSN
- 0892-3973
1532-2513
- 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. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
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Collections - College of Medicine > College of Medicine > 1. Journal Articles
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