Lack of Association of a Functional Polymorphism in the Interleukin 8 Gene with Susceptibility to Periodontitis

Kim, Yeon Jung; Viana, Aline Cavalcanti; Curtis, Karen M. C.; Orrico, Silvana Regina Perez; Cirelli, Joni Augusto; Scarel‐Caminaga, Raquel Mantuaneli

doi:10.1089/dna.2008.0816

Cited by 34 publications

(45 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When the three SNPs were analyzed together as haplotypes, we found a significant association between the haplotypes and periodontitis susceptibility (Tables 4 and 5). Similar findings were observed with the same population in a previous study (Kim et al, 2009) and in other studies of Brazilian individuals in which IL10 and a vitamin D receptor (de Brito Junior et al, 2004) were examined. These previous studies corroborate the idea that haplotypes are more powerful in detecting susceptibility alleles than individual polymorphisms and that they may give more information on the disease.…”

Section: Discussionsupporting

confidence: 91%

“…These findings were also obtained in the multivariate analysis. Similar results were also obtained in a previous study investigating the association of a polymorphism in the IL8 gene with periodontitis in the same population (Kim et al, 2009). It has been established that smoking habits are an important risk factor for the initiation and progression of periodontitis (Genco, 1996;Kornman, 2005;Gonzales et al, 2007).…”

Section: Discussionsupporting

confidence: 81%

“…The exclusion criteria for enrolling patients in the study were use of prophylactic antibiotics, chronic usage of antiinflammatory drugs, current pregnancy, ongoing orthodontic therapy, and self-declared history of diseases that influence the immune system, diabetes mellitus, HIV infection, or immunosuppressive chemotherapy (Kim et al, 2009). Each subject was examined by one of two calibrated periodontists, who carried out the periodontal examinations throughout the study period (weighted kappa ¼ 0.74, considering the probing depth [PD]).…”

Section: Selection Of Subjectsmentioning

confidence: 99%

See 2 more Smart Citations

Association of Haplotypes in theCXCR2Gene with Periodontitis in a Brazilian Population

Viana

Kim

Curtis

et al. 2010

DNA and Cell Biology

Self Cite

View full text Add to dashboard Cite

CXCR-2 is a receptor of interleukin-8, which is involved in acute and chronic inflammatory processes. Polymorphisms in the CXCR2 gene have been associated with chronic inflammatory conditions. The aim of this study was to investigate whether the þ785(C=T), þ1208(T=C), and þ1440(G=A) single-nucleotide polymorphisms (SNPs) in the CXCR2 gene, as well as their haplotypes, are associated with susceptibility to periodontitis in Brazilians. DNA was extracted from the buccal epithelial cells of 487 individuals (control ¼ 215; periodontitis ¼ 272). The SNPs were investigated using the sequence-specific primer-polymerase chain reaction method. Associations between the polymorphisms and subject phenotypes were analyzed using the chi-squared statistical test, followed by univariate and multivariate logistic regression modeling. Haplotypes were reconstructed using the expectation-maximization algorithm, and differences in haplotype distribution between the groups were analyzed to estimate genetic susceptibility for periodontitis development. Univariate and multivariate analysis revealed that age, skin color, and smoking status were associated with periodontitis. The þ1440 GG genotype was shown to be protective against periodontitis in both univariate and multivariate analysis (odds ratio [OR] adjusted ¼ 0.42; 95% confidence interval [CI] ¼ 0.19, 0.96). A similar relevant result for the þ1440 GG was obtained in an alternative analysis considering a subgroup containing only white nonsmokers (OR ¼ 0.37; 95% CI ¼ 0.15, 0.92). White nonsmokers with the CTG=TCG haplotype appeared to be genetically protected against the development of periodontitis (OR ¼ 0.29; 95% CI ¼ 0.09, 0.89), while those carrying the CTG=TCA haplotype were more susceptible to the development of periodontitis (OR ¼ 2.08; 95% CI ¼ 1.24, 3.51). In conclusion, the þ1440 SNP and some haplotypes are associated with periodontitis in Brazilian individuals.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 81%

Section: Selection Of Subjectsmentioning

confidence: 99%

See 1 more Smart Citation

Association of Haplotypes in theCXCR2Gene with Periodontitis in a Brazilian Population

Viana

Kim

Curtis

et al. 2010

DNA and Cell Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Downregulation of the innate immune response promotes host-microbe homeostasis and highly orchestrated expression, of certain host defense mediators and cytokines is associated with healthy periodontal tissues (13). High concentrations of IL-8 have been found in gingival crevicular fluid from periodontitis patients, suggesting an important role for this potent chemokine in disease pathogenesis (21). In our study we observed a high level of IL-8 production by naïve and tolerized human monocytes treated with P. gingivalis LPS.…”

Section: Discussionsupporting

confidence: 64%

Impaired Immune Tolerance toPorphyromonas gingivalisLipopolysaccharide Promotes Neutrophil Migration and Decreased Apoptosis

et al. 2010

View full text Add to dashboard Cite

Periodontitis, a chronic inflammatory disease of the tissues supporting the teeth, is characterized by an exaggerated host immune and inflammatory response to periopathogenic bacteria. Toll-like receptor activation, cytokine network induction, and accumulation of neutrophils at the site of inflammation are important in the host defense against infection. At the same time, induction of immune tolerance and the clearance of neutrophils from the site of infection are essential in the control of the immune response, resolution of inflammation, and prevention of tissue destruction. Using a human monocytic cell line, we demonstrate that Porphyromonas gingivalis lipopolysaccharide (LPS), which is a major etiological factor in periodontal disease, induces only partial immune tolerance, with continued high production of interleukin-8 (IL-8) but diminished secretion of tumor necrosis factor alpha (TNF-␣) after repeated challenge. This cytokine response has functional consequences for other immune cells involved in the response to infection. Primary human neutrophils incubated with P. gingivalis LPS-treated naïve monocyte supernatant displayed a high migration index and increased apoptosis. In contrast, neutrophils treated with P. gingivalis LPS-tolerized monocyte supernatant showed a high migration index but significantly decreased apoptosis. Overall, these findings suggest that induction of an imbalanced immune tolerance in monocytes by P. gingivalis LPS, which favors continued secretion of IL-8 but decreased TNF-␣ production, may be associated with enhanced migration of neutrophils to the site of infection but also with decreased apoptosis and may play a role in the chronic inflammatory state seen in periodontal disease.

show abstract

“…Differences in IB proteins degradation have also been reported by Martin et al (40) who observed maintained degradation of IB-␤ after repeated challenge by P. gingivalis LPS but not E. coli LPS. High concentrations of IL-8 have been found in gingival crevicular fluid from periodontitis patients, suggesting an important role for this potent chemokine in the disease pathogenesis (41). Furthermore, Muthukuru et al (42) reported that monocytes from periodontitis patients were more resistant to down-regulation of IL-8 production after repeated challenge with P. gingivalis LPS compared with other cytokines.…”

Section: Discussionmentioning

confidence: 99%

Altered Toll-like Receptor 2-mediated Endotoxin Tolerance Is Related to Diminished Interferon β Production

Zarić

Coulter

Shelburne

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Induction of endotoxin tolerance leads to a reduced inflammatory response after repeated challenge by LPS and is important for resolution of inflammation and prevention of tissue damage. Enterobacterial LPS is recognized by the TLR4 signaling complex, whereas LPS of some non-enterobacterial organisms is capable of signaling independently of TLR4 utilizing TLR2-mediated signal transduction instead. In this study we report that Porphyromonas gingivalis LPS, a TLR2 agonist, fails to induce a fully endotoxin tolerant state in a human monocytic cell line (THP-1) and mouse bone marrow-derived macrophages. In contrast to significantly decreased production of human IL-8 and TNF-␣ and, in mice, keratinocyte-derived cytokine (KC), macrophage inflammatory protein-2 (MIP-2), and TNF-␣ after repeated challenge with Escherichia coli LPS, cells repeatedly exposed to P. gingivalis LPS responded by producing less TNF-␣ but sustained elevated secretion of IL-8, KC, and MIP-2. Furthermore, in endotoxin-tolerant cells, production of IL-8 is controlled at the signaling level and correlates well with NF-B activation, whereas TNF-␣ expression is blocked at the gene transcription level. Interferon ␤ plays an important role in attenuation of chemokine expression in endotoxin-tolerized cells as shown in interferon regulatory factor-3 knock-out mice. In addition, human gingival fibroblasts, commonly known not to display LPS tolerance, were found to be tolerant to repeated challenge by LPS if pretreated with interferon ␤. The data suggest that the inability of the LPS-TLR2 complex to induce full endotoxin tolerance in monocytes/macrophages is related to diminished production of interferon ␤ and may partly explain the involvement of these LPS isoforms in the pathogenesis of chronic inflammatory diseases.Detection of pathogen-associated molecular patterns by Toll-like receptors (TLRs) 2 expressed on innate immune cells triggers a robust and essential inflammatory reaction. Inflammation as a well coordinated process that comprises increased vascular permeability, migration of polymorphonuclear leukocytes, monocytes, and lymphocytes into affected tissues, and activation of cells to secrete inflammatory mediators is essential for host defense (1). If it is well controlled and resolved in a timely manner, it benefits the host by elimination of the invading pathogen. Otherwise, prolonged or excessive inflammation leads to chronicity and tissue damage (2).Toll-like receptors represent a family of evolutionarily highly conserved transmembrane molecules that act as pathogen recognition receptors. To date, 13 mammalian TLRs have been identified, and each appears to be required for responses to a different class of infectious pathogen (3). Almost immediately after microbes invade, microbial products signal through TLRs, broadly distributed on immune cells, activating these cells to produce proinflammatory cytokines, interferons, histamine, and antimicrobial peptides (4). Toll-like receptor signaling represents a principal molecular pathway for host in...

show abstract

Lack of Association of a Functional Polymorphism in the Interleukin 8 Gene with Susceptibility to Periodontitis

Cited by 34 publications

References 36 publications

Association of Haplotypes in theCXCR2Gene with Periodontitis in a Brazilian Population

Association of Haplotypes in theCXCR2Gene with Periodontitis in a Brazilian Population

Impaired Immune Tolerance toPorphyromonas gingivalisLipopolysaccharide Promotes Neutrophil Migration and Decreased Apoptosis

Altered Toll-like Receptor 2-mediated Endotoxin Tolerance Is Related to Diminished Interferon β Production

Contact Info

Product

Resources

About