Positive Health Online

Abstract

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

9. Department of Immunoallergy, Salamanca University Hospital, Salamanca, Spain conducted a study  analyze the effect of Retinoic acid (RA), a metabolite of Vitamin A, on the activation of the promoter region of the PTGDR gene, a receptor of PGD2 in the prostaglandin pathway.

Background

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.

Methodology

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.

Conclusion

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.

References

García-Sánchez A1,2, Marcos-Vadillo E2,3, Sanz C2,4, Hernández-Hernández L2, Cerutti-Müller G5, Marqués-García F2,3, Lorente F6,2,7, Isidoro-García M2,3,8, Dávila I6,2,9. Retinoic Acid Modulates PTGDR Promoter Activity. J Investig Allergol Clin Immunol 26(4):249-55. 2016. doi: 10.18176/jiaci.0042   Epub Apr 11 2016.