title: 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.
authors.affiliation: Karolinska Institutet, Division of Periodontology, Department of Dental Medicine, Stockholm, Sweden.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Boström
authors.affiliation: Umeå University, Department of Molecular Periodontology, Umeå, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Kindstedt
authors.affiliation: Umeå University, Department of Molecular Periodontology, Umeå, Sweden.
authors.forename: Rima
authors.initials: R
authors.lastname: Sulniute
authors.affiliation: Umeå University, Department of Molecular Periodontology, Umeå, Sweden.
authors.forename: Py
authors.initials: P
authors.lastname: Palmqvist
authors.affiliation: Karolinska Institutet, Division of Periodontology, Department of Dental Medicine, Stockholm, Sweden.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Majster
authors.affiliation: Umeå University, Department of Molecular Periodontology, Umeå, Sweden.
authors.forename: Cecilia Koskinen
authors.initials: CK
authors.lastname: Holm
authors.affiliation: Karolinska Institutet, Division of Periodontology, Department of Dental Medicine, Stockholm, Sweden.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zwicker
authors.affiliation: Karolinska Institutet, Division of Periodontology, Department of Dental Medicine, Stockholm, Sweden.
authors.forename: Reuben
authors.initials: R
authors.lastname: Clark
authors.affiliation: Umeå University, Department of Molecular Periodontology, Umeå, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Önell
authors.affiliation: Umeå University, Department of Cariology, Umeå, Sweden.
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Johansson
authors.affiliation: Umeå University, Department of Molecular Periodontology, Umeå, Sweden; University of Gothenburg, Sahlgrenska Academy, Centre for Bone and Arthritis Research, Gothenburg, Sweden.
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
authors.affiliation: Umeå University, Department of Molecular Periodontology, Umeå, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Lundberg
mesh_terms: D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D002097:C-Reactive Protein; D054413:Chemokine CCL11 / Q000097:blood / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000097:blood* / Q000473:pathology; D010519:Periodontium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012907:Smoking
chemical_list: C111835:CCL2 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D016207:Cytokines; D002097:C-Reactive Protein