GLUCOCORTICOIDS INDUCE BOTH DECREASED UPTAKE OF Ox-LDL AND CHOLESTEROL EFFLUX IN THP1 MACROPHAGES. ROLE OF 11β HYDROXYSTEROID DEHYDROGENASE TYPE 1.

GONZALEZ MARINA CECILIA; LEDDA, ANGELO; GULFO J; DÍAZ LUDOVICO IVO; JUAN D. TOLEDO; HORACIO A. GARDA; GRASA, MARÍA DEL MAR; ESTEVE RAFOLS, MONTSERRAT

Puerto iguazú, Misiones

Conferencia; 56th International Conference on the Bioscience of Lipids (ICBL); 2015

ICBL

Human monocytes THP1cells were transformed into macrophages by adding PMA in the culture medium.Isolated LDL fraction from human plasma was peroxidized in vitro with Cu++ totransform LDL into Ox-LDL. Macrophages THP1 cells were treated for 24 h withOx-LDL and different concentrations (0.1nM to 1000nM) of cortisol or cortisone,the last in presence or not of BVT.2733, an inhibitor of the enzyme 11ßHSD1involved in the conversion of cortisone into cortisol. The expression of genesmacrophage markers (F4/80, TNFα, MMR), of OxLDL uptake (FAT/CD36), of esterificationof cholesterol (ACAT) and of efflux of cholesterol (LXRα, ABC-A1, ABC-G1 andApoE) were evaluated by RT-PCR as indicators of inflammation and lipid accumulation.Also the gene expression of 11ßHSD1 was evaluated. The presence of Ox-LDL provokedthe increase of all genes studied except for MMR, which showed a deepdown-regulation. Cortisol promoted a doses-dependent decrease expression of allgenes, except for MMR where there was a marked increase. Cortisone had noeffect on MMR and on the rest of genes studied cortisone only mimics thecortisol effects at highest concentrations tested. The presence of the11ßHSD1inhibitor BTV.2733 prevented cortisone action in all cases. Our resultsindicate a direct effect of glucocorticoid in the macrophages, decreasing theuptake of OxLDL and the re-esterification of cholesterol but also inhibitingthe output of cholesterol through inhibition of reverse cholesterol transport.In addition, the 11βHSD1 activity in macrophages could have a relevant role inatherogenic progression.