The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
| Autor: | Dias, Fabrício C., Bertol, Bruna C., Poras, Isabelle, Souto, Bruno M., Mendes-Junior, Celso T., Castelli, Erick C. [UNESP], Gineau, Laure, Sabbagh, Audrey, Rouas-Freiss, Nathalie, Carosella, Edgardo D., Donadi, Eduardo A., Moreau, Philippe |
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| Přispěvatelé: | Universidade de São Paulo (USP), Hôpital Saint-Louis, Universidade Estadual Paulista (Unesp), COMUE Sorbonne Paris-Cité |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| Popis: | Made available in DSpace on 2018-12-11T17:19:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-01 The HLA-G 5'URR extending 1.4 kb from the ATG presents a unique set of regulatory elements among HLA genes. Several variable sites have been described that coincide with or are close to these elements, thus HLA-G 5′URR polymorphism might influence the HLA-G expression level. We cloned the ten most frequent HLA-G 5′URR haplotypes to evaluate their activity on a luciferase reporter gene in HLA-G+ cell lines (JEG-3/choriocarcinoma and FON+/melanoma). We also investigated associations between the plasma HLA-G (sHLA-G) levels and the HLA-G 5′URR variability in 157 healthy individuals. Cell lines were transfected with pGL3-Basic vector constructions containing HLA-G 5′URR sequences. The G010101a (in JEG-3) and G010101b (in FON+) haplotypes exhibited higher promoter activity, whereas the G010101d (in JEG-3) and G010102a (in FON+) haplotypes exhibited lower promoter activity. In the presence of HLA-G inducers (interferon-β and progesterone) or repressors (cyclopamine) HLA-G promoter activity was modulated, but certain haplotypes exhibited differential responses. No strict association was observed between plasma sHLA-G levels and the 5′URR haplotypes or genotypes; however, the G010101b haplotype was underrepresented among HLA-G-negative plasmas. Therefore, the HLA-G 5′URR polymorphism may have an impact on the modulation of HLA-G gene expression, but alone provides a limited predictive value for sHLA-G levels in vivo. Department of Medicine Division of Clinical Immunology Faculty of Medicine of Ribeirão Preto University of São Paulo Commissariat À l'Energie Atomique et Aux Energies Alternatives Direction de la Recherche Fondamentale Institut de Biologie François Jacob Service de Recherches en Hémato-Immunologie Hôpital Saint-Louis Université Paris-Diderot Sorbonne Paris-Cité UMR-E5 Institut Universitaire d'Hématologie Hôpital Saint-Louis Department of Biochemistry and Immunology Faculty of Medicine of Ribeirão Preto University of São Paulo Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo São Paulo State University (UNESP) Department of Pathology School of Medicine Botucatu State of São UMR 216-MERIT Institut de Recherche pour le Développement Faculté de Pharmacie de Paris Université Paris Descartes COMUE Sorbonne Paris-Cité São Paulo State University (UNESP) Department of Pathology School of Medicine Botucatu State of São |
| Databáze: | OpenAIRE |
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