Decreased Ox-LDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1

LEDDA, ANGELO; GONZALEZ MARINA CECILIA (SENIOR AUTHOR); GULFO J; DÍAZ LUDOVICO IVO; RAMELLA NAHUEL; JUAN D. TOLEDO; HORACIO A. GARDA; GRASA, MARÍA DEL MAR(SENIOR AUTHOR); ESTEVE, MONTSERRAT(SENIOR AUTHOR)

ATHEROSCLEROSIS

ELSEVIER IRELAND LTD

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

0021-9150

Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol 1 and by cortisone through 11β-hydroxysteroid dehydrogenase type 1Angelo Ledda, Marina Gonzalez§, José Gulfo, Ivo Díaz Ludovico, Nahuel Ramella, Juan Toledo, Horacio Garda, Mar Grasa §, and Montserrat Esteve §ǂ Department of Nutrition and Food Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain  CIBER Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain INIBIOLP-CONICET, Facultad Cs. Médicas, Universidad Nacional de La Plata, La Plata, Argentina § These authors contributed equally to this work and should be considered as senior authorsAbstract Background and Aims. Data about glucocorticoids role in the development of atherosclerosis are controversial showing different effects in human than in experimental animal models. Atherosclerosis is the result of a chronic inflammatory response to an injured endothelium where  an uncontrolled uptake of OxLDL by macrophages triggers the development of foam cells, the  main component of fatty streaks in atherosclerotic plaque. There are few data about the direct effect of glucocorticoids in macrophages of atherosclerotic plaque. The aim of the study was to  elucidate the role of glucocorticoids in the development of foam cells in atherosclerosis initiation.  Methods. For this purpose we used THP1 cells differentiated to macrophages with phorbol esters and incubated with OxLDL alone or with cortisol or cortisone. THP1 cells were also incubated with cortisone plus an inhibitor of 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) activity to determine the role of this enzyme on glucocorticoid action in this process. Results. Ours results showed that cortisol and cortisone decreased significantly the inflammation promoted by OxLDL, and also diminished the expression of genes involved in influx and efflux of cholesterol resulting in a reduced lipid accumulation. Likewise cortisol and cortisone decreased  11βHSD1 expression in THP1 cells. The presence of the inhibitor of 11βHSD1 abolished all the effects elicited by cortisone.  Conclusion. Our results indicate a direct effect of glucocorticoids on macrophages braking atherosclerosis initiation, reducing pro-inflammatory markers and OxLDL uptake and cholesterol re-esterification, but also inhibiting cholesterol output. These effects appear to be mediated, at least in part, by 11βHSD1 activity.