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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Functional Haplotypes in Interleukin 4 Gene Associated with Periodontitis

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Anovazzi, Giovana ; de Medeiros, Marcell Costa ; Pigossi, Suzane Cristina ; Finoti, Livia Sertori ; Alves Mayer, Marcia Pinto ; Rossa Junior, Carlos ; Scarel-Caminaga, Raquel Mantuaneli
Total Authors: 7
Document type: Journal article
Source: PLoS One; v. 12, n. 1 JAN 23 2017.
Web of Science Citations: 3

Chronic periodontitis (CP) is an infectious inflammatory disease that affects tooth-supporting structures and in which dental plaque bacteria, immune mechanisms and genetic predisposition play important roles. Interleukin 4 (IL-4) is a key anti-inflammatory cytokine with relevant action in imbalances in inflamed periodontal tissue. Individuals carrying the TCI/CCI genotype (S-haplotype) of the IL-4 gene are 5 times more susceptible to CP, whereas the CTI/TTD genotype (P-haplotype) confers protection against CP. Compared with the S-haplotype, subjects with the P-haplotype produce higher levels of the IL-4 protein after non-surgical periodontal therapy. The present in vitro study aimed to investigate the functionality of IL-4 haplotypes in immune cells to obtain insight into the influence of these genetic variations in regulating immune responses to CP-associated bacteria. Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens to compare responses of the different haplotypes with regard to gene expression, protein secretion and the immunophenotype of T helper responses. We found higher IL-4 mRNA and protein levels in the P-haplotype, which also presented higher levels of anti-inflammatory cytokines. In contrast, cells from S-haplotype subjects responded with higher levels of pro-inflammatory cytokines. S-haplotype individuals exhibited significantly greater polarization toward the Th1 phenotype, whereas the Phaplotype was associated with an attenuated response to periodontopathogens, with suggestive skewing toward Th2/M2 phenotypes. In conclusion, IL-4 genetic variations associated with susceptibility to or protection against chronic periodontitis are directly associated with influencing the response of immune cells to periodontopathogens. (AU)

FAPESP's process: 14/04638-2 - Investigation of the functional role of haplotypes in the interleukin 4 gene
Grantee:Giovana Anovazzi Medeiros
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/17887-8 - Investigation of the functional role of haplotypes in the interleukin 4 and interleukin 8 genes
Grantee:Raquel Mantuaneli Scarel Caminaga
Support type: Regular Research Grants