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Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines.

Boström EA, Kindstedt E, Sulniute R, Palmqvist P, Majster M, Holm CK, Zwicker S, Clark R, Önell S, Johansson I, Lerner UH, Lundberg P - PLoS ONE (2015)

Bottom Line: Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin.We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable.Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation.

View Article: PubMed Central - PubMed

Affiliation: Karolinska Institutet, Division of Periodontology, Department of Dental Medicine, Stockholm, Sweden.

ABSTRACT
Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss.

No MeSH data available.


Related in: MedlinePlus

Multivariate PLS modeling results in a model with clustered periodontitis cases from periodontally healthy and significantly enhanced levels of inflammatory mediators in serum from periodontally diseased.(A) PLS scatter plot illustrating separation of periodontally diseased from healthy subjects by their serum concentrations of inflammatory markers and subject characteristics (see labels in B). The scores t1 and t2 are the new PCS created variables summarizing the x variables; (B) PLS column loading plot showing PLS correlation coefficients with 95% CI for the variables in the model, i.e. the model behind the separation in A. Bars for which the 95% whisker does not pass zero are statistically significant. Serum levels of eotaxin (pg/ml) (C), MCP-1 (pg/ml) (D), and CRP (mg/l) (E) in individuals with periodontitis and in periodontally healthy. Data are presented as arithmetic means (eotaxin and MCP-1) or geometric mean (CRP) with 95% confidence intervals. To circumvent confounding by BMI, data for MCP-1 and CRP are presented in BMI strata, i.e. BMI<25, BMI 25–30, BMI>30.
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pone.0134608.g001: Multivariate PLS modeling results in a model with clustered periodontitis cases from periodontally healthy and significantly enhanced levels of inflammatory mediators in serum from periodontally diseased.(A) PLS scatter plot illustrating separation of periodontally diseased from healthy subjects by their serum concentrations of inflammatory markers and subject characteristics (see labels in B). The scores t1 and t2 are the new PCS created variables summarizing the x variables; (B) PLS column loading plot showing PLS correlation coefficients with 95% CI for the variables in the model, i.e. the model behind the separation in A. Bars for which the 95% whisker does not pass zero are statistically significant. Serum levels of eotaxin (pg/ml) (C), MCP-1 (pg/ml) (D), and CRP (mg/l) (E) in individuals with periodontitis and in periodontally healthy. Data are presented as arithmetic means (eotaxin and MCP-1) or geometric mean (CRP) with 95% confidence intervals. To circumvent confounding by BMI, data for MCP-1 and CRP are presented in BMI strata, i.e. BMI<25, BMI 25–30, BMI>30.

Mentions: Multivariate PLS modeling employing serum concentration of all analyzed inflammatory markers, and a set of subject characteristics resulted in a model, which clustered periodontitis patients from periodontally healthy subjects (Fig 1A). The explanatory power (R2) was 54.4% and the cross validated predictive power (Q2) 44.3%. Concentrations of CRP, eotaxin, and MCP-1, in addition to years of smoking and age, were significantly associated with periodontitis, whereas more own teeth and high education were associated with being periodontally healthy (Fig 1B). No clustering of present versus never smokers was found by PCA employing the serum cytokines and chemokines (S1 Fig). Exclusion of outliers did not alter the result.


Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines.

Boström EA, Kindstedt E, Sulniute R, Palmqvist P, Majster M, Holm CK, Zwicker S, Clark R, Önell S, Johansson I, Lerner UH, Lundberg P - PLoS ONE (2015)

Multivariate PLS modeling results in a model with clustered periodontitis cases from periodontally healthy and significantly enhanced levels of inflammatory mediators in serum from periodontally diseased.(A) PLS scatter plot illustrating separation of periodontally diseased from healthy subjects by their serum concentrations of inflammatory markers and subject characteristics (see labels in B). The scores t1 and t2 are the new PCS created variables summarizing the x variables; (B) PLS column loading plot showing PLS correlation coefficients with 95% CI for the variables in the model, i.e. the model behind the separation in A. Bars for which the 95% whisker does not pass zero are statistically significant. Serum levels of eotaxin (pg/ml) (C), MCP-1 (pg/ml) (D), and CRP (mg/l) (E) in individuals with periodontitis and in periodontally healthy. Data are presented as arithmetic means (eotaxin and MCP-1) or geometric mean (CRP) with 95% confidence intervals. To circumvent confounding by BMI, data for MCP-1 and CRP are presented in BMI strata, i.e. BMI<25, BMI 25–30, BMI>30.
© Copyright Policy
Related In: Results  -  Collection

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pone.0134608.g001: Multivariate PLS modeling results in a model with clustered periodontitis cases from periodontally healthy and significantly enhanced levels of inflammatory mediators in serum from periodontally diseased.(A) PLS scatter plot illustrating separation of periodontally diseased from healthy subjects by their serum concentrations of inflammatory markers and subject characteristics (see labels in B). The scores t1 and t2 are the new PCS created variables summarizing the x variables; (B) PLS column loading plot showing PLS correlation coefficients with 95% CI for the variables in the model, i.e. the model behind the separation in A. Bars for which the 95% whisker does not pass zero are statistically significant. Serum levels of eotaxin (pg/ml) (C), MCP-1 (pg/ml) (D), and CRP (mg/l) (E) in individuals with periodontitis and in periodontally healthy. Data are presented as arithmetic means (eotaxin and MCP-1) or geometric mean (CRP) with 95% confidence intervals. To circumvent confounding by BMI, data for MCP-1 and CRP are presented in BMI strata, i.e. BMI<25, BMI 25–30, BMI>30.
Mentions: Multivariate PLS modeling employing serum concentration of all analyzed inflammatory markers, and a set of subject characteristics resulted in a model, which clustered periodontitis patients from periodontally healthy subjects (Fig 1A). The explanatory power (R2) was 54.4% and the cross validated predictive power (Q2) 44.3%. Concentrations of CRP, eotaxin, and MCP-1, in addition to years of smoking and age, were significantly associated with periodontitis, whereas more own teeth and high education were associated with being periodontally healthy (Fig 1B). No clustering of present versus never smokers was found by PCA employing the serum cytokines and chemokines (S1 Fig). Exclusion of outliers did not alter the result.

Bottom Line: Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin.We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable.Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation.

View Article: PubMed Central - PubMed

Affiliation: Karolinska Institutet, Division of Periodontology, Department of Dental Medicine, Stockholm, Sweden.

ABSTRACT
Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss.

No MeSH data available.


Related in: MedlinePlus