title: 7-Keto-cholesterol and 25-hydroxy-1 cholesterol rapidly enhance ROS production in human neutrophils.
abstract: OBJECTIVE
  Oxysterols are cholesterol-oxygenated derivatives generated in the organism and also present in foods because of cholesterol oxidation during processing and storage. They are the natural ligands of liver X receptors (LXRs) and are generally recognized as hypocholesterolemic and anti-inflammatory molecules although this latter property is still controversial. Most oxysterol studies have been performed in macrophages, whereas the effects of oxysterols in neutrophils are poorly known. In this study, human neutrophils were exposed to two different oxysterols, 7-keto-cholesterol (7-k-chol) and 25-hydroxy-cholesterol (25-OH-chol), and their possible participation in inflammatory process was evaluated.
  
  
  METHODS
  Human neutrophils were incubated with 7-k-chol and 25-OH-chol, and ROS production, translocation of the NADPH oxidase cytosolic components, hemoxygenase-1 (HO-1) expression and lysozyme secretion were analyzed.
  
  
  RESULTS
  An increase in ROS production was observed within a short period of time (minutes) with both molecules. These oxysterols also stimulated the cellular membrane translocation of the NADPH oxidase cytosolic components, p47phox and p67phox. On the other hand, HO-1 expression, a cytoprotector enzyme, is inhibited in human neutrophils upon oxysterols treatment. Moreover, both oxysterols were associated with high lysozyme enzyme secretion at 5 and 18 h of incubation.
  
  
  CONCLUSIONS
  The present paper describes for the first time that two oxysterols (7-k-chol and 25-OH-chol) enhance the ROS production within a short period of time in human neutrophils, stimulate the translocation of the cytosolic components of NADPH oxidase to the cellular membrane and increase lysozyme secretion. These data suggest that both oxysterols are able to activate pro-inflammatory effects in human neutrophils which contrasts with the role assigned to the oxysterols when they act through LXR at long time of incubation.
authors.affiliation: Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Seville, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Alba
authors.affiliation: Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Seville, Spain.
authors.forename: María Edith
authors.initials: ME
authors.lastname: Reyes-Quiróz
authors.affiliation: Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Seville, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sáenz
authors.affiliation: Hospital Nuestra Señora de Valme, Servicio Andaluz de Salud, Seville, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Geniz
authors.affiliation: Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Seville, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Jiménez
authors.affiliation: Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Martín-Nieto
authors.affiliation: Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Seville, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pintado
authors.affiliation: Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Seville, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sobrino
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, C/Profesor García González 2, 41012, Seville, Spain. csm@us.es.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Santa-María
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007653:Ketocholesterols / Q000494:pharmacology*; D009113:Muramidase / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D006888:Hydroxycholesterols; D007653:Ketocholesterols; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; C079789:neutrophil cytosol factor 67K; C007997:25-hydroxycholesterol; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; D009113:Muramidase; C003001:7-ketocholesterol
keywords: Hemoxygenase-1; Lipid metabolism; Neutrophils; Oxysterols; Radical oxygen species