Functionality and opposite roles of two interleukin 4 haplotypes in immune cells
| Autor: | C Rossa-Junior, T M Souza Moreira, Giovana Anovazzi, Cleslei Fernando Zanelli, Marcell Costa de Medeiros, Raquel M. Scarel-Caminaga, Suzane Cristina Pigossi, Sandro Roberto Valentini, Marcia Pinto Alves Mayer, Livia S. Finoti |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Genotype Immunology Immunogenetics Biology Real-Time Polymerase Chain Reaction 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Gene expression Genetics Humans Genetic Predisposition to Disease Promoter Regions Genetic Gene Genetics (clinical) Interleukin 4 Inflammation Polymorphism Genetic Haplotype Promoter Prognosis 030104 developmental biology Haplotypes chemistry Case-Control Studies Chronic Periodontitis Ionomycin Original Article Female Interleukin-4 REAÇÃO EM CADEIA POR POLIMERASE Biomarkers Follow-Up Studies 030215 immunology |
| Zdroj: | Genes and Immunity Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1476-5470 1466-4879 |
| DOI: | 10.1038/gene.2016.47 |
| Popis: | Cytokines expression can be influenced by polymorphisms in their respective coding genes. We associated the CTI/TTD haplotype (Hap-1) and TCI/CCI haplotype (Hap-2) in the IL4 gene formed by the -590, +33 and variable number of tandem repeat polymorphisms with the severity of chronic periodontitis in humans. The functionality of these IL4 haplotypes in the response of immune cells to phorbol 12-myristate 13-acetate (PMA) with Ionomycin and IL-1β (as inflammatory stimuli) was evaluated. Gene expression (quantitative real-time PCR), profile of secreted cytokines (multiplex) and phenotypic polarization of T cells (flow cytometry) were the outcomes assessed. Green fluorescent protein reporter plasmid constructs containing specific IL4 haplotype were transiently transfected into JM cells to assess the influence of the individual haplotypes on promoter activity. In response to inflammatory stimuli the immune cells from Hap-1 haplotype had increased expression of anti-inflammatory IL4; conversely, the Hap-2 haplotype showed higher levels of pro-inflammatory cytokines. The haplotype CTI proved to be the most important for the regulation of IL4 promoter, regardless of the nature of the inflammatory stimulation; whereas the polymorphism in the promoter region had the least functional effect. In conclusion, IL4 haplotypes studied are functional and trigger opposite immune responses: anti-inflammatory (Hap-1) and pro-inflammatory (Hap-2). In addition, we identified the CTI haplotype as the main responsible for the regulation of IL4 transcriptional activity. |
| Databáze: | OpenAIRE |
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