The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
We have previously demonstrated that 1α,25 dihydroxy-vitamin D3 (1α,25(OH)2D3) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)2D3 exerts its...
| Autores: | , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2012 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/62541 |
| Acceso en línea: | http://hdl.handle.net/11336/62541 |
| Access Level: | acceso abierto |
| Palabra clave: | Nfkb 1α,25(Oh)2-Vitamin D3 Endothelial Cells Kaposi Sarcoma https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| Sumario: | We have previously demonstrated that 1α,25 dihydroxy-vitamin D3 (1α,25(OH)2D3) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)2D3 exerts its growth inhibitory effects by inhibiting the Nuclear Factor κ B (NFκB) pathway which is highly activated by vGPCR. Cell proliferation studies demonstrated that 1α,25(OH)2D3, similarly to bortezomib, a proteosome inhibitor that suppresses the activation of NFκB, reduced the proliferation of endothelial cells transformed by vGPCR (SVEC-vGPCR). The activity of NFκB in these cells decreased by 70% upon 1α,25(OH)2D3 treatment. Furthermore, time and dose response studies showed that the hormone significantly decreased NFκB and increased IκBα mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IκBα increased significantly. Moreover, NFκB translocation to the nucleus was inhibited and occurred by a mechanism independent of NFκB association with vitamin D3 receptor (VDR). 1α,25(OH)2D3-induced increase in IκBα required de novo protein synthesis, and was independent of MAPK and PI3K/Akt pathways. Altogether, these results suggest that down-regulation of the NFκB pathway is part of the mechanism involved in the antiproliferative effects of 1α,25(OH)2D3 on endothelial cells transformed by vGPCR. |
|---|