Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines.
Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines.
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DOI：
10.1371/journal.pone.0134608
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lundberg P
中科院分区：
文献类型：
--
作者：
Boström EA;Kindstedt E;Sulniute R;Palmqvist P;Majster M;Holm CK;Zwicker S;Clark R;Önell S;Johansson I;Lerner UH;Lundberg P
牙周炎是一种牙齿支持组织的慢性炎症性疾病，导致牙周组织破坏，最终可能导致牙齿脱落。该病的特点是持续的白细胞浸润，可能是由局部产生的趋化因子介导的，但其致病机制尚未完全阐明。目前还没有可靠的血清学生物标志物用于牙周炎的诊断，目前牙周炎的诊断完全基于局部组织破坏的程度，也没有可用的生物治疗工具。由于对牙周炎和全身炎症介质的兴趣日益增加，我们绘制了牙周炎受试者和健康对照组的血清细胞因子和趋化因子水平。我们使用多元偏最小二乘法(PLS)建模，发现单核细胞趋化蛋白-1(MCP-1)和嗜酸性粒细胞趋化因子与牙周炎以及C-反应蛋白(CRP)、吸烟年限和年龄明显相关，而剩余牙齿的数量与健康相关。此外，体重指数与血清MCP-1和CRP显著相关，但与嗜酸性粒细胞趋化因子无关。我们检测到炎症牙龈结缔组织中MCP-1蛋白水平高于健康人，但未检测到嗜酸性粒细胞趋化蛋白水平。原代培养的人牙龈成纤维细胞在肿瘤坏死因子-α和白介素1-α(IL-1β，IL-1β)刺激下，牙周组织中单核细胞趋化蛋白-1和嗜酸性粒细胞趋化因子基因和蛋白的表达显著增加。我们还证明，趋化因子的上调表达依赖于NF-κΒ途径。综上所述，我们发现牙周炎患者血清中的C反应蛋白、嗜酸性粒细胞趋化因子和单核细胞趋化蛋白-1水平较高。这一点，加上我们发现CRP和MCP-1都与BMI相关，表明牙周炎和高BMI患者的全身炎症负荷增加。在牙周炎中靶向嗜酸性粒细胞趋化因子和单核细胞趋化蛋白-1可能会减少牙周炎中的白细胞浸润和炎症，并可能防止牙齿脱落。
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.