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

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.

Association Between Marginal Jawbone Loss and Onset of Rheumatoid Arthritis and Relationship to Plasma Levels of RANKL

“…In periodontitis, tooth‐related bacteria evoke gingival inflammation, which in disease‐susceptible individuals may cause a loss of jawbone . Patients with progressive periodontitis have elevated serum levels of C‐reactive protein , a finding that supports the hypothesis that periodontal inflammation causes a systemic load in these patients. The mechanisms of induction of RA remain unclear, but autoantibodies and increased concentrations of proinflammatory and antiinflammatory cytokines are known to predate the onset of disease symptoms .…”

Histone deacetylases 1 and 2 inhibition suppresses cytokine production and osteoclast bone resorption in vitro

“…2,3 Investigations assessing inflammation related bone pathologies have utilized the procatabolic features of cytokines such as TNF, to establish in vitro techniques that represent this stimulated environment and the formation of inflammatory osteoclasts. [5][6][7] A number of studies have demonstrated increased expression and production of these molecules in inflamed periodontal gingival tissues and crevicular fluids in PD, 8,9 and synovial samples from human or mouse models of RA, [10][11][12] supporting a need to reduce both the immune response and the activity of inflammatory osteoclasts. [5][6][7] A number of studies have demonstrated increased expression and production of these molecules in inflamed periodontal gingival tissues and crevicular fluids in PD, 8,9 and synovial samples from human or mouse models of RA, [10][11][12] supporting a need to reduce both the immune response and the activity of inflammatory osteoclasts.…”

Patients with tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) are hypersensitive to Toll-like receptor 9 stimulation

“…In addition, our results also revealed increased serum levels of IFN‐γ, IL‐17 and IL‐22, suggestive of additional proinflammatory responses, most probably from NK and T cell populations and of VEGF and the pleotrophic cytokine TGF‐β, although their relevance in TRAPS disease pathology is currently unclear. The raised levels of MCP‐1 seen in patients may be a consequence of the elevated IL‐1‐β, IL‐6 and TNF‐α and may have some bearing on muscle inflammation in TRAPS . Our findings from patient sera therefore highlight the complexity of the constitutive inflammatory status of TRAPS patients, even when clinically well and maintained on a cytokine neutralization therapy that does not target the central disease mechanisms .…”