Functional Haplotypes in Interleukin 4 Gene Associ... - BV FAPESP
Advanced search
Start date
Betweenand
Related content
(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

Full text
Author(s):
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
Abstract

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 Opportunities: 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 Opportunities: Regular Research Grants