Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, 513 Parnassus Street, San Francisco, CA 94143, Box 0422, USA.
BMC Immunol. 2011 Jan 24;12:9. doi: 10.1186/1471-2172-12-9.
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.
牙齿对龋齿的免疫反应始于成牙本质细胞识别致龋细菌。炎症的传播最终导致牙髓坏死和健康危害。本研究旨在确定体内龋齿引起的人牙中细胞因子基因表达谱，并构建这些反应和下游信号网络的机制模型。
我们证明了体内龋齿患者牙本质细胞层（ODL）中炎症基因的显著差异上调，而牙髓基本保持不变。在龋齿牙齿的 ODL 中，白细胞介素、趋化因子及其所有测试的受体均差异上调，其中 84 个基因中有 35 个上调超过 100 倍。通过询问对应差异上调基因的重构蛋白相互作用网络，我们提出假设，即在龋齿牙齿的 ODL 中高度表达的促炎细胞因子 IL-1β、IL-1α 和 TNF-α，携带趋化的炎症信号。我们表明，IL1β 在体外刺激牙本质细胞中抗菌肽的产生，比脂多糖高 100 倍，其方式与随后的体内测量相匹配。
我们的数据表明，ODL 通过自身反馈细胞因子-趋化因子信号-受体循环，以及通过 IL1R1 并可能通过其他受体进行信号汇聚，戏剧性地放大细菌信号，以增加防御能力，包括抗菌肽的产生，从而保护牙齿并控制牙本质内龋齿细菌的战斗。
