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/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

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/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

Hypokalemic periodic paralysis is a rare disorder characterized by sudden onset of weakness and low serum potassium levels. We report a case provoked by combination chemotherapy including prednisolone. A 23-yr-man, diagnosed with diffuse large B-cell lymphoma, received chemotherapy. He developed significant weakness in upper and lower extremities during chemotherapy, and his serum potassium level was 1.7 mmol/L. Potassium replacement restored the weakness. Further workup revealed that prednisolone had provoked hypokalemic paralysis. As prednisolone triggered an attack of hypokalemic periodic paralysis, it should be administered with caution, particularly in patients with periodic paralysis.
Drug Therapy ; Drug Therapy, Combination ; Humans ; Hypokalemic Periodic Paralysis ; Lower Extremity ; Lymphoma, B-Cell* ; Paralysis* ; Potassium ; Prednisolone

Hypokalemic periodic paralysis is a rare disorder characterized by sudden onset of weakness and low serum potassium levels. We report a case provoked by combination chemotherapy including prednisolone. A 23-yr-man, diagnosed with diffuse large B-cell lymphoma, received chemotherapy. He developed significant weakness in upper and lower extremities during chemotherapy, and his serum potassium level was 1.7 mmol/L. Potassium replacement restored the weakness. Further workup revealed that prednisolone had provoked hypokalemic paralysis. As prednisolone triggered an attack of hypokalemic periodic paralysis, it should be administered with caution, particularly in patients with periodic paralysis.
Drug Therapy ; Drug Therapy, Combination ; Humans ; Hypokalemic Periodic Paralysis ; Lower Extremity ; Lymphoma, B-Cell* ; Paralysis* ; Potassium ; Prednisolone