Investigation of the functional role of human Interleukin-8 gene haplotypes by CRISPR/Cas9 mediated genome editing

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorBenakanakere, Manjunatha R.-
Autor(es): dc.creatorFinoti, Livia S.-
Autor(es): dc.creatorTanaka, Urara-
Autor(es): dc.creatorGrant, Gregory R.-
Autor(es): dc.creatorScarel-Caminaga, Raquel M.-
Autor(es): dc.creatorKinane, Denis F.-
Data de aceite: dc.date.accessioned2021-03-11T00:41:24Z-
Data de disponibilização: dc.date.available2021-03-11T00:41:24Z-
Data de envio: dc.date.issued2018-12-11-
Data de envio: dc.date.issued2018-12-11-
Data de envio: dc.date.issued2016-08-08-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1038/srep31180-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/173330-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/173330-
Descrição: dc.descriptionNational Institute of Dental and Craniofacial Research-
Descrição: dc.descriptionInterleukin-8 (IL-8) gene polymorphisms have been considered as susceptibility factors in periodontal disease. However, the functional roles of IL-8 gene haplotypes have not been investigated. Here, we demonstrate for the first time the use of the CRISPR/Cas9 system to engineer the IL-8 gene, and tested the functionality of different haplotypes. Two sgRNAs vectors targeting the IL-8 gene and the naked homologous repair DNA carrying different haplotypes were used to successfully generate HEK293T cells carrying the AT genotype at the first SNP-rs4073 (alias-251), TT genotype at the second SNP-rs2227307 (alias +396), TC or CC genotypes at the third SNP-rs2227306 (alias +781) at the IL-8 locus. When stimulated with Poly I:C, ATC/TTC haplotype, cells significantly up-regulated the IL-8 at both transcriptional and translational levels. To test whether ATC/TTC haplotype is functional, we used a trans-well assay to measure the transmigration of primary neutrophils incubated with supernatants from the Poly I:C stimulation experiment. ATC/TTC haplotype cells significantly increased transmigration of neutrophils confirming the functional role for this IL-8 haplotype. Taken together, our data provides evidence that carriage of the ATC/TTC haplotype in itself may increase the influx of neutrophils in inflammatory lesions and influence disease susceptibility.-
Idioma: dc.languageen-
Relação: dc.relationScientific Reports-
Relação: dc.relation1,533-
Direitos: dc.rightsopenAccess-
Título: dc.titleInvestigation of the functional role of human Interleukin-8 gene haplotypes by CRISPR/Cas9 mediated genome editing-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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