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Retinoic Acid Modulates PTGDR Promoter Activity

García-Sánchez A1,2, Marcos-Vadillo E2,3, Sanz C2,4, Hernández-Hernández L2, Cerutti-Müller G5, Marqués-García F2,3, Lorente F1,2,6, Isidoro-García M2,3,7, Dávila I1,2,8

1Department of Biomedical and Diagnostic Science, University of Salamanca, Salamanca, Spain
2Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain
3Department of Clinical Biochemistry, Salamanca University Hospital, Salamanca, Spain
4Department of Microbiology and Genetics, University of Salamanca, Spain
5Universidade do Vale do Rio dos Sinos-UNISINOS, São Leopoldo, Brazil
6Department of Pediatrics, Salamanca University Hospital, Salamanca, Spain
7Department of Medicine, University of Salamanca, Salamanca, Spain
8Department of Immunoallergy, Salamanca University Hospital, Salamanca, Spain

J Investig Allergol Clin Immunol 2016; Vol 26(4) : 249-255
doi: 10.18176/jiaci.0042

Background and 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.

Key words: Allergic asthma, Polymorphisms, PTGDR, Retinoic acid.