Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11 beta -hydroxysteroid dehydrogenase type 1

ANGELO LEDDA; MARINA GONZÁLEZ; JOSE  GULFO; IVO DÍAZ LUDOVICO; NAHUEL RAMELLA ; JUAN TOLEDO; HORACIO GARDA; MAR GRASA; MONTSERRAT ESTEVE

ATHEROSCLEROSIS

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2016 vol. 250 p. 84 - 94

0021-9150

Background and aims: Data about glucocorticoids role in the development of atherosclerosis arecontroversial showing different effects in human than in experimental animal models. Atherosclerosis isthe result of a chronic inflammatory response to an injured endothelium where an uncontrolled uptakeof OxLDL by macrophages triggers the development of foam cells, the main component of fatty streaks inatherosclerotic plaque. There are few data about the direct effect of glucocorticoids in macrophages ofatherosclerotic plaque. The aim of the study was to elucidate the role of glucocorticoids in the devel-opment of foam cells in atherosclerosis initiation.Methods: For this purpose we used THP1 cells differentiated to macrophages with phorbol esters andincubated with OxLDL alone or with cortisol or cortisone. THP1 cells were also incubated with cortisoneplus an inhibitor of 11 b -hydroxysteroid dehydrogenase 1 (11 b HSD1) activity to determine the role of thisenzyme on glucocorticoid action in this process.Results: Ours results showed that cortisol and cortisone decreased significantly the inflammation pro-moted by OxLDL, and also diminished the expression of genes involved in influx and efflux of cholesterolresulting in a reduced lipid accumulation. Likewise cortisol and cortisone decreased 11 b HSD1 expressionin THP1 cells. The presence of the inhibitor of 11 b HSD1 abolished all the effects elicited by cortisone.Conclusion: Our results indicate a direct effect of glucocorticoids on macrophages braking atherosclerosisinitiation, reducing pro-inflammatory markers and OxLDL uptake and cholesterol re-esterification, butalso inhibiting cholesterol output. These effects appear to be mediated, at least in part, by 11 b HSD1activity.