title: Retinoic Acid Modulates PTGDR Promoter Activity.
abstract: OBJECTIVE
  Vitamin A has been linked to the development of allergic diseases although its role is not fully understood, Retinoic acid (RA), a metabolite of Vitamin A, has been previously associated with the prostaglandin pathway, and PTGDR, a receptor of PGD2, has been proposed as a candidate gene in allergy and asthma. Considering the role of PTGDR in allergy, the goal of this study was to analyze the effect of RA on the activation of the promoter region of the PTGDR gene.
  
  
  METHODS
  A549 lung epithelial cells were transfected with 4 combinations of genetic variants of the PTGDR promoter and stimulated with all-trans RA (ATRA); luciferase assays were performed using the Dual Luciferase Reporter System, and real-time quantitative polymerase chain reaction was used to measure the expression of PTGDR, CYP26A1, RARA, RARB, RARG, and RXRA in basal A549 cell cultures and after ATRA treatment. We also performed an in silico analysis.
  
  
  RESULTS
  After ATRA treatment increased expression of CYP26A1 (12-fold) and RARB (4-fold) was detected. ATRA activated PTGDR promoter activity in transfected cells (P<.001) and RA response element sequences were identified in silico in this promoter region.
  
  
  CONCLUSIONS
  RA modulated PTGDR promoter activity. Differential response to RA and to new treatments based on PTGDR modulation could depend on genetic background in allergic asthmatic patients.
authors.affiliation: 1Department of Biomedical and Diagnostic Science, University of Salamanca, Salamanca, Spain.|Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: García-Sánchez
authors.affiliation: Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.|Department of Clinical Biochemistry, Salamanca University Hospital, Salamanca, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Marcos-Vadillo
authors.affiliation: Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.|Department of Microbiology and Genetics, University of Salamanca, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Sanz
authors.affiliation: Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Hernández-Hernández
authors.affiliation: Universidade do Vale do Rio dos Sinos-UNISINOS, São Leopoldo, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Cerutti-Müller
authors.affiliation: Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.|Department of Clinical Biochemistry, Salamanca University Hospital, Salamanca, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Marqués-García
authors.affiliation: Department of Biomedical and Diagnostic Science, University of Salamanca, Salamanca, Spain.|Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.|Department of Pediatrics, Salamanca University Hospital, Salamanca, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Lorente
authors.affiliation: Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.|Department of Clinical Biochemistry, Salamanca University Hospital, Salamanca, Spain.|Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Isidoro-García
authors.affiliation: Department of Biomedical and Diagnostic Science, University of Salamanca, Salamanca, Spain.|Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain.|Department of Immunoallergy, Salamanca University Hospital, Salamanca, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Dávila
mesh_terms: D024506:5' Flanking Region; D001665:Binding Sites; D045744:Cell Line, Tumor; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011971:Receptors, Immunologic / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014212:Tretinoin; C036293:prostaglandin D2 receptor
keywords: Allergic asthma; PTGDR; Polymorphisms; Retinoic acid