title: Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ledda
authors.affiliation: INIBIOLP-CONICET, Facultad Cs. Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: González
authors.affiliation: 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.
authors.forename: José
authors.initials: J
authors.lastname: Gulfo
authors.affiliation: INIBIOLP-CONICET, Facultad Cs. Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Ivo
authors.initials: I
authors.lastname: Díaz Ludovico
authors.affiliation: INIBIOLP-CONICET, Facultad Cs. Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Nahuel
authors.initials: N
authors.lastname: Ramella
authors.affiliation: INIBIOLP-CONICET, Facultad Cs. Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Toledo
authors.affiliation: INIBIOLP-CONICET, Facultad Cs. Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Garda
authors.affiliation: 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.
authors.forename: Mar
authors.initials: M
authors.lastname: Grasa
authors.affiliation: 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. Electronic address: mesteve@ub.edu.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Esteve
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003348:Cortisone / Q000097:blood* / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000378:metabolism; D007249:Inflammation; D008077:Lipoproteins, LDL / Q000097:blood*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D000074084:THP-1 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone; D006854:Hydrocortisone
keywords: 11β-hydroxysteroid dehydrogenase 1; 11β-hydroxysteroid dehydrogenase 2; Cortisol; Cortisone; Foam cells; THP1 macrophages