Differential chemokine response of fibroblast subtypes to complement C1q.
Differential chemokine response of fibroblast subtypes to complement C1q.
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DOI：
10.1111/j.1600-0765.2006.00916.x
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发表时间：
2007-02
影响因子：
3.5
通讯作者：
S. Verardi;R. C. Page;Ammons Wf;S. Bordin
中科院分区：
文献类型：
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作者：
S. Verardi;R. C. Page;Ammons Wf;S. Bordin
背景与目的牙周炎的发病机制包括经典补体级联反应（C′）的不适当激活以及炎症C′产物在液体和组织中的积累。我们的假设是，在体内，C'产物C1q可能作为不同基质成纤维细胞对炎症环境的先天免疫反应的调节成分。本研究分析了C1q诱导来自不同牙周组织的成纤维细胞亚型中促炎细胞因子的分泌，并确定了细胞反应的机制。材料与方法用C1q处理原代人牙龈成纤维细胞、牙周韧带成纤维细胞和肉芽组织成纤维细胞培养24 h。蛋白质阵列评估了组成型和c1q诱导型促炎细胞因子的分泌谱，酶联免疫吸附法用于量化每种诱导型细胞因子的动力学。结果肉芽组织成纤维细胞培养对C1q无反应。相比之下，牙周韧带成纤维细胞的单核细胞化学引诱蛋白(MCP)-1、白细胞介素-6、白细胞介素-8和巨噬细胞炎症蛋白(MIP)-1 β的释放分别比基础水平高8.2倍、7.0倍、3.8倍和7.2倍。人牙龈成纤维细胞培养使这些趋化因子的分泌分别增加了5.2倍、4.5倍、3.0倍和9.8倍。抑制剂研究表明，c1q诱导的趋化因子在人牙龈成纤维细胞和牙周韧带培养物中的释放取决于p38丝裂原激活的蛋白激酶活性。结论C1q刺激促炎趋化因子分泌的能力与具体的成纤维细胞亚型有关。靶向c1q激活的细胞内信号通路可能是抑制促进炎症细胞浸润到牙龈和牙周韧带组织的趋化因子产生的有效手段。
BACKGROUND AND OBJECTIVE The pathogenesis of periodontitis includes an inappropriate activation of the classical complement cascade (C') with accumulation of inflammatory C' products in fluids and tissues. Our hypothesis is that in vivo the C' product, C1q, may act as a regulatory component of the innate immune response of distinct matrix fibroblasts to the inflammatory environment. This study analyzed the C1q induction of pro-inflammatory cytokine secretion in fibroblast subtypes derived from distinct periodontal tissues, and identified a mechanism of the cell response. MATERIAL AND METHODS Primary human gingival fibroblast, periodontal ligament fibroblast, and granulation tissue fibroblast cultures were treated for 24 h with C1q. Protein arrays assessed the secretory profile of constitutive and C1q-inducible pro-inflammatory cytokines, and enzyme-linked immunosorbent assays were used to quantify the kinetics of each inducible cytokine. RESULTS Granulation tissue fibroblast cultures were unresponsive to C1q challenge. In contrast, periodontal ligament fibroblasts responded with a release of monocyte chemoattractant protein (MCP)-1, interleukin-6, interleukin-8, and macrophage inflammatory protein (MIP)-1beta higher than the basal level by 8.2-, 7.0-, 3.8-, and 7.2-fold, respectively. Human gingival fibroblast cultures increased secretion of these chemokines by 5.2-, 4.5-, 3.0-, and 9.8-fold, respectively. Inhibitor studies revealed that C1q-inducible release of chemokines by the human gingival fibroblast and periodontal ligament cultures was contingent upon p38 mitogen-activated protein kinase activity. CONCLUSION The ability of C1q to stimulate secretion of pro-inflammatory chemokines depends upon which specific fibroblast subtype is involved. Targeting C1q-activated intracellular signaling pathways may be an effective means to inhibit the production of chemokines that promote inflammatory cell infiltration into gingival and periodontal ligament tissues.