SOCS3 is an inducible endogenous negative regulator of JAK/STAT pathway, which is relevant in inflammatory conditions. We used a model of LPS-induced periodontal disease in rats to correlate SOCS3 expression with the inflammatory status. In vitro we used a murine macrophage cell line to assess the physical interaction between SOCS3 and STAT3 by coimmunoprecipitation. 30 ug of LPS from Escherichia coli were injected in the gingival tissues on the palatal aspect of first molars of the animals 3x/week for up to 4 weeks. Control animals were injected with the vehicle (PBS). The rats were sacrificed at 7, 15, and 30 days. Inflammation and gene expression were assessed by stereometric analysis, immunohistochemistry, RT-qPCR, and western blot. LPS injections increased inflammation, paralleled by an upregulation of SOCS3, of the proinflammatory cytokines IL-1β, IL-6, and TNF-α and increased phosphorylation of STAT3 and p38 MAPK. SOCS3 expression accompanied the severity of inflammation and the expression of proinflammatory cytokines, as well as the activation status of STAT3 and p38 MAPK. LPS stimulation in a macrophage cell line in vitro induced transient STAT3 activation, which was inversely correlated with a dynamic physical interaction with SOCS3, suggesting that this may be a mechanism for SOCS3 regulatory function.

The important inflammatory mediator interleukin-8 (IL-8) is responsible for the migration and activation of neutrophils. The IL8 gene contains a functional single-nucleotide polymorphism (SNP) (rs4073) in its promoter region that may influence the expression of IL-8, and which has been associated with inflammatory diseases. The purpose of this study was to investigate the association of the SNP (rs4073) in the IL8 gene with susceptibility to periodontitis. DNA was extracted from the buccal epithelial cells of 500 individuals (control n ¼ 224 and periodontitis n ¼ 276). Individuals were genotyped for the SNP (rs4073) using sequence-specific primer polymerase chain reaction. Associations between the SNP (rs4073) and subject phenotypes were analyzed using the chisquared test, followed by univariate and multivariate logistic regression modeling. The genotype distributions in both groups were consistent with Hardy-Weinberg equilibrium. Univariate and multivariate analysis showed that age, skin color, and smoking status were associated with periodontitis. No significant differences were found for sex and frequencies of alleles and genotypes between the control and periodontitis groups in the univariate analysis. These findings were replicated in the multivariate analysis. The SNP (rs4073) in the IL8 gene is not associated with susceptibility to periodontitis in Brazilian individuals, even after controlling for covariates.

Interleukin-8 (IL-8), which is responsible for the migration and activation of neutrophils, is an important inflammatory mediator involved in the initiation and amplification of acute inflammatory reactions and chronic inflammatory processes. IL-8 plays an important role in periodontitis, an inflammatory disease characterized by the loss of connective tissue and alveolar bone. The aim of this study was to investigate whether the SNPs rs2227307 (+396) and rs2227306 (+781), and the haplotypes they formed together with the previously investigated rs4073 (-251), were associated with chronic periodontitis susceptibility. Clinical periodontal exams were performed and DNA samples were collected from 493 individuals (223 with periodontitis and 270 controls). Associations between SNPs, haplotypes, and subject phenotypes were analyzed using the χ(2) test followed by multivariate logistic regression modeling. We conclude that the +396TT genotype and the haplotypes ATC/TTC and AGT/TGC were significantly associated with chronic periodontitis susceptibility in Brazilians.

Significant associations between alleles, genotypes, and haplotypes of polymorphisms in the IL4 gene and chronic periodontitis were verified in Brazilian individuals.