XAV939, a Wnt/ß-catenin pathway modulator, has inhibitory effects on LPS-induced inflammatory response.
Immunopharmacol Immunotoxicol
; 41(3): 394-402, 2019 Jun.
Article
em En
| MEDLINE
| ID: mdl-30466341
ABSTRACT
Aim:
In this study, we report the anti-inflammatory activity of XAV939, a modulator of the Wnt/ß-catenin pathway.Methods:
WNT/ß-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-1ß, 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 ß-catenin, which shows that the anti-inflammatory effect of XAV939 is mediated by the modulation of ß-catenin, a central component of the WNT/ß-catenin pathway.Conclusion:
The findings of this study showed that XAV939 exerts anti-inflammatory effects through the modulation of the Wnt/ß-catenin pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Lipopolissacarídeos
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Células Endoteliais da Veia Umbilical Humana
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Via de Sinalização Wnt
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Compostos Heterocíclicos com 3 Anéis
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Anti-Inflamatórios
Limite:
Humans
Idioma:
En
Revista:
Immunopharmacol Immunotoxicol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article