INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Glucocorticoids induce both decreased uptake of ox-LDL and cholesterol efflux in THP1 macrophages. Role of 11-beta hydroxysteroid dehydrogenase type 1
Autor/es:
GONZALEZ MC; LEDDA A; GULFO J; DÍAZ LUDOVICO I; TOLEDO JD; GARDA HA; GRASA M; ESTEVE M
Lugar:
Puerto Iguazú, Misiones
Reunión:
Congreso; 56th International Conference on the Bioscience of Lipids (ICBL); 2015
Institución organizadora:
ICBL
Resumen:
Human monocytes THP1 cells were transformed into macrophages by adding PMA in theculture médium. Isolated LDL fraction from human plasma was peroxidized invitro with Cu++ to transform LDL into Ox-LDL. Macrophages THP1 cells weretreated for 24 h with Ox-LDL and different concentrations (0.1 nM to 1000 nM)of cortisol or cortisone, the last in presence or not of BVT.2733, an inhibitorof the enzyme 11βHSD1 involved in the conversion of cortisone into cortisol.The expression of genes macrophage markers (F4/80, TNFa, MMR), of Ox-LDL uptake (FAT/CD36), ofesterification of cholesterol (ACAT) and of efflux of cholesterol (LXRa, ABC-A1, ABC-G1 and ApoE) were evaluated byRT-PCR as indicators of inflammation and lipid accumulation. Also the geneexpression of 11βHSD1 was evaluated. The presence of Ox-LDL provoked theincrease of all genes studied except for MMR , which showed a deepdownregulation. Cortisol promoted a doses-dependent decreased expression of allgenes, except for MMR where there was a marked increase.Cortisone had no effecton MMR and on the rest of genes studied, cortisone only mimics the cortisoleffects at highest concentration tested. The presence of the 11βHSD1 inhibitor BVT.2733prevented cortisone action in all cases. Our results indicate a direct effectof glucocorticoid in the macrophages, decreasing the uptake of Ox-LDL and there-esterification of cholesterol but also inhibiting the output of cholesterolthrough inhibition of reverse cholesterol transport. In addition, the 11βHSD1activity in macrophages could have a relevant role in atherogenic progression.