COX-2 REGULATION BY 1α,25(OH)2D3-VDR LIGAND IN ENDOTHELIAL CELLS EXPRESSING vGPCR.

TAPIA, C; SUARES, A; GONZALEZ PARDO, V; SALVADOR, G

Buenos Aires

Congreso; LIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)- Reunión Conjunta de Sociedades de Biociencias; 2017

COX-2 REGULATION BY 1α,25(OH)2D3-VDR LIGAND IN ENDOTHELIAL CELLS EXPRESSING vGPCR. Abstract: The Kaposi?s Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. 1α,25(OH)2D3 anti-proliferative impact in vGPCR cells occur in part by NF-κB pathway negative modulation, family of conserved transcription factors critical during the pro-inflammatory response. In this work, we studied if COX-2 regulation by 1α,25(OH)2D3 in vGPCR cells contributes to the anti-inflammatory action. As we have previously reported vGPCR cell proliferation is inhibited by 1α,25(OH)2D3 (10 nM, 48 h) due to a reduction on cells number, PLA2 inhibitor ATK (10-20 µM) or the COX-2 inhibitor Celecoxib (10-20 µM) decreases vGPCR cell number in a dose dependent manner, similarly to 1α,25(OH)2D3. These changes are accompanied by morphological modifications observed at the microscope. qRT-PCR analysis of COX-2 gene expression revealed a mRNA increase within 20 min of 1α,25(OH)2D3 treatment and remains increased at least for 72 h. Moreover, ATK inhibitor (20µM) could not counteract COX-2 mRNA induced by 1α,25(OH)2D3 (10 nM, 24 h). Finally, COX-2 VDR dependence was evaluated using the stable VDR knock-down cell line vGPCR-shVDR; COX-2 mRNA increment by 1α,25(OH)2D3 is found impaired in these cells. Significant differences of the data between control (vehicle) and treated conditions were analyzed by one way-ANOVA followed by Bonferroni test or t-test (*p< 0.05, **p