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

Elisabeth A Boström,Elin Kindstedt,Cecilia Koskinen Holm,Pernilla Lundberg,Ingegerd Johansson,Ulf H Lerner,Py Palmqvist,Reuben Clark,Sebastian Önell,Stephanie Zwicker,Mirjam Majster,Rima Sulniute,David M Ojcius

doi:10.1371/journal.pone.0134608

Elisabeth A Boström, Elin Kindstedt + Show 11 more

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https://doi.org/10.1371/journal.pone.0134608

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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.

Highlights

Periodontitis is characterized by loss of tooth supporting tissues driven by a local chronic inflammation
As the distribution between groups regarding age and smoking was skewed we assessed the correlations between eotaxin or MCP-1 and smoking and age, respectively, we found no significant correlations
Despite the evolving field of defective systemic host response in periodontitis and the link to atherosclerosis [3] and rheumatoid arthritis (RA) [6], few serologic markers have been identified and little is known about periodontal disease susceptibility

Summary

Introduction

Periodontitis is characterized by loss of tooth supporting tissues driven by a local chronic inflammation. The fact that the severity of tissue destruction varies between individuals suggests that intrinsic differences in the host-response affect how the inflammatory process causes loss of tooth supporting tissues, including jawbone [1]. Increasing evidence suggests that periodontitis is reflected by an oral and by a systemic increase in inflammatory mediators [2]. This may contribute to the reported relation to other inflammation associated conditions such as atherosclerosis [3], diabetes [4], increased body mass index (BMI) [5], and rheumatoid arthritis (RA) [6]. The cellular- and molecular pathogenetic mechanisms of periodontitis are complex and still elusive which is displayed by the lack of established local or systemic biological markers

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