KMID : 0811720210250040307
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Korean Journal of Physiology & Pharmacology 2021 Volume.25 No. 4 p.307 ~ p.319
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Wnt-C59 inhibits proinflammatory cytokine expression by reducing the interaction between ¥â-catenin and NF-¥êB in LPS-stimulated epithelial and macrophage cells
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Jang Jae-Woong
Song Jae-Won Sim In-Ae Yoon Yoo-Sik
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Abstract
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Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson¡¯s disease, Alzheimer¡¯s disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/¥â-catenin pathway in LPS stimulated cells was suppressed by Wnt- C59 treatment. The level of ¥â-catenin, the executor protein of Wnt/¥â-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of ¥â-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-¥êB) activity. We found that the interaction between ¥â-catenin and NF-¥êB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-¥êB activity for its target DNA binding and the reporter activity of NF-¥êB-responsive promoter showed identical patterns with the interaction between ¥â-catenin and NF-¥êB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of ¥â-catenin and the interaction between ¥â-catenin and NF-¥êB, which results in the suppressions of the NF-¥êB activity and proinflammatory cytokine expression.
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KEYWORD
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Catenins, Cytokines, Inflammation, NF-kappa B
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