PeproTech Inc.
Originally published online as doi:10.1189/jlb.0308184 on August 25, 2008

Published online before print August 25, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0308184v1
84/6/1565    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Claudino, M.
Right arrow Articles by Garlet, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Claudino, M.
Right arrow Articles by Garlet, G. P.
(Journal of Leukocyte Biology. 2008;84:1565-1573.)
© 2008 by Society for Leukocyte Biology

The broad effects of the functional IL-10 promoter-592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome

Marcela Claudino*, Ana Paula F. Trombone{dagger}, Cristina R. Cardoso{dagger}, Samuel B. Ferreira, Jr*, Walter Martins, Jr{ddagger}, Gerson F. Assis*, Carlos F. Santos*, Paula C. Trevilatto§, Ana Paula Campanelli*, João S. Silva{dagger} and Gustavo P. Garlet*,1

* Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, São Paulo, Brazil;
{dagger} Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil;
{ddagger} Department of Periodontics, Dentistry School of University of Ribeirão Preto, Ribeirão Preto, Brazil; and
§ School of Dentistry, Pontifical Catholic University of Paraná, Curitiba, Brazil

1 Correspondence: Bauru School of Dentistry (FOB/USP), Department of Biological Sciences, Al. Octávio Pinheiro Brisolla, 9-75, Bauru, SP 17012-901, Brazil. E-mail: garletgp{at}usp.br

Periodontal diseases are infectious diseases, in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. It occurs through the generation of metalloproteinases and the activation of bone resorption mechanisms. Anti-inflammatory cytokines such as IL-10 seem to attenuate periodontal tissue destruction through the induction of tissue inhibitors of metalloproteinases (TIMPs) and the inhibitor of osteoclastogenesis osteoprotegerin (OPG). A high individual variation in levels of IL-10 mRNA is verified in periodontitis patients, which is possibly determined by genetic polymorphisms. In this study, the IL-10 promoter -592C/A single nucleotide polymorphism (SNP), which is associated with a decrease in IL-10 production, was analyzed by RFLP in 116 chronic periodontitis (CP) patients and 173 control (C) subjects, and the IL-10, TIMPs, and OPG mRNA expression levels in diseased gingival tissues were determined by real-time-PCR. The IL-10-592 SNP CA (P=0.0012/OR=2.4/CI:1.4-4.1), AA (P=0.0458/OR=2.3/CI:1.1-4.9), and CA+AA (P=0.0006/OR=2.4/CI:1.4-3.4) genotypes and the allele A (P=0.0036/OR=1.7/CI:1.2-2.4) were found to be significantly more prevalent in the CP group when compared with control subjects. Both CA and AA genotypes were associated with lower levels of IL-10, TIMP-3, and OPG mRNA expression in diseased periodontal tissues and were also associated with disease severity as mean pocket depth. Taken together, the results presented here demonstrate that IL10-592 SNP is functional in CP, being associated with lower levels of IL-10 mRNA expression, which is supposed to consequently decrease the expression of the downstream genes TIMP-3 and OPG, and influence periodontal disease outcome.

Key Words: interleukin-10 • genetic polymorphism • single nucleotide polymorphism • cytokine • immunoregulation • osteoprotegerin • periodontal disease