NFkB PATHWAY IS DOWN-REGULATED BY 1,25(OH)2 -VITAMIN D3 IN ENDOTHELIAL CELLS TRANSFORMED BY KAPOSI SARCOMA ASSOCIATED HERPES VIRUS G PROTEIN COUPLED RECEPTOR

VERONICA GONZALEZ PARDO; NOELIA D' ELIA; ANNEMIEKE VERSTUYF; RICARDO BOLAND; ANA RUSSO DE BOLAND

STEROIDS

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2012 vol. 77 p. 1025 - 1032

0039-128X

We have previously demonstrated that 1a,25 dihydroxy-vitamin D3 (1a,25(OH)2D3) has antiproliferativeeffects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated toKaposi sarcoma (vGPCR). In this work, we have investigated whether 1a,25(OH)2D3 exerts its growthinhibitory effects by inhibiting the Nuclear Factor j B (NFjB) pathway which is highly activated by vGPCR.Cell proliferation studies demonstrated that 1a,25(OH)2D3, similarly to bortezomib, a proteosome inhibitorthat suppresses the activation of NFjB, reduced the proliferation of endothelial cells transformed byvGPCR (SVEC-vGPCR). The activity of NFjB in these cells decreased by 70% upon 1a,25(OH)2D3 treatment.Furthermore, time and dose response studies showed that the hormone significantly decreased NFjB andincreased IjBa mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IjBa increased significantly.Moreover, NFjB translocation to the nucleus was inhibited and occurred by a mechanism independentof NFjB association with vitamin D3 receptor (VDR). 1a,25(OH)2D3-induced increase in IjBa requiredde novo protein synthesis, andwas independent of MAPK and PI3K/Akt pathways. Altogether, these resultssuggest that down-regulation of the NFjB pathway is part of the mechanism involved in the antiproliferativeeffects of 1a,25(OH)2D3 on endothelial cells transformed by vGPCR.