Caries induced cytokine network in the odontoblast layer of human teeth.
Caries induced cytokine network in the odontoblast layer of human teeth.
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DOI：
10.1186/1471-2172-12-9
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发表时间：
2011-01-24
期刊：
影响因子：
3
通讯作者：
Dale BA
中科院分区：
文献类型：
--
作者：
Horst OV;Horst JA;Samudrala R;Dale BA
牙齿对龋病的免疫反应始于成牙本质细胞识别龋病细菌。炎症扩散最终导致牙髓坏死，危害健康。本研究旨在确定活体内人类牙齿对龋病的反应所产生的细胞因子基因表达谱，并建立这些反应和下游信号网络的机制模型。我们在活体实验中证明，在患龋齿的人牙齿中，牙髓中的炎症基因在成牙本质层(ODL)中有显著的差异上调，而牙髓基本保持不变。白细胞介素类、趋化因子和所有被测试的受体在龋齿的ODL中都有不同程度的上调，在84个基因中有35个基因上调了100倍以上。通过查询与差异上调基因相对应的重构的蛋白质相互作用网络，我们提出了一个假设，即在龋齿的ODL中高表达的促炎细胞因子IL-1β、IL-1α和肿瘤坏死因子-α携带着聚合的炎症信号。我们发现，IL-1β在体外扩增成牙本质细胞中抗菌肽的产量是脂多糖的100倍以上，这一方式与随后的体内测量相匹配。我们的数据表明，ODL通过自我反馈的细胞因子-趋化因子信号-受体循环，以及通过IL1R1和其他可能的信号收敛，大幅放大细菌信号，以增加防御能力，包括抗菌肽的产生，以保护牙齿和遏制对抗牙本质中的龋齿细菌的战斗。
Immunologic responses of the tooth to caries begin with odontoblasts recognizing carious bacteria. Inflammatory propagation eventually leads to tooth pulp necrosis and danger to health. The present study aims to determine cytokine gene expression profiles generated within human teeth in response to dental caries in vivo and to build a mechanistic model of these responses and the downstream signaling network. We demonstrate profound differential up-regulation of inflammatory genes in the odontoblast layer (ODL) in human teeth with caries in vivo, while the pulp remains largely unchanged. Interleukins, chemokines, and all tested receptors thereof were differentially up-regulated in ODL of carious teeth, well over one hundred-fold for 35 of 84 genes. By interrogating reconstructed protein interaction networks corresponding to the differentially up-regulated genes, we develop the hypothesis that pro-inflammatory cytokines highly expressed in ODL of carious teeth, IL-1β, IL-1α, and TNF-α, carry the converged inflammatory signal. We show that IL1β amplifies antimicrobial peptide production in odontoblasts in vitro 100-fold more than lipopolysaccharide, in a manner matching subsequent in vivo measurements. Our data suggest that ODL amplifies bacterial signals dramatically by self-feedback cytokine-chemokine signal-receptor cycling, and signal convergence through IL1R1 and possibly others, to increase defensive capacity including antimicrobial peptide production to protect the tooth and contain the battle against carious bacteria within the dentin.
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影响因子：
4.2
作者：
Bettaccini AA;Baj A;Accolla RS;Basolo F;Toniolo AQ
通讯作者：
Toniolo AQ
影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
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2.8
作者：
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通讯作者：
Farges, Jean-Christophe
DOI：
10.1016/j.bbadis.2005.03.007
发表时间：
2005-09-25
影响因子：
6.2
作者：
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通讯作者：
Cooper, PR
影响因子：
3.2
作者：
Ota, Masao;Katsuyama, Yoshihiko;Kawa, Shigeyuki
通讯作者：
Kawa, Shigeyuki