Differential regulation of immune responses by odontoblasts
Differential regulation of immune responses by odontoblasts
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DOI：
10.1111/j.1399-302x.2007.00310.x
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发表时间：
2007-02-01
影响因子：
--
通讯作者：
Dale, B. A.
中科院分区：
文献类型：
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作者：
Veerayutthwilai, O.;Byers, M. R.;Dale, B. A.
成牙本质细胞（OBs）是排列在牙齿内表面的细胞。它们在牙齿内宿主防御中的潜在作用是通过它们产生抗菌β-防御素来暗示的，但它们的作用需要确认。本研究旨在确定人类OBs在微生物识别和先天宿主反应中的作用。Toll样受体2（TLR 2）和TLR 4，以及CCR 6，免疫定位在人类OBs和他们的牙本质过程中原位。为了检查OB功能，我们使用器官型牙冠培养物将人类OB维持在其牙本质支架内。培养和非培养的牙冠制备物的OB层中的细胞表达了几种先天免疫标记物的mRNA，包括趋化因子CCL 20、趋化因子受体CCR 6、TLR 2、TLR 4和OB标记物牙本质唾液磷蛋白（DSPP）。人β-防御素1（hBD 1）、hBD 2、hBD 3、白细胞介素-8（IL-8）和CCL 20的表达随着培养时间的推移而增加。牙冠成牙本质细胞（TcOB）培养物用特异于TLR 2（Pam 3CSK 4）或TLR 4 [大肠杆菌脂多糖（LPS）]的激动剂刺激。核因子-κ B分析证实了Pam 3CSK 4的TLR 2活性和LPS的TLR 4活性。LPS上调IL-1 β、肿瘤坏死因子-α（TNF-α）、CCL 20、hBD 2、IL-8、TLR 2和TLR 4;然而，Pam 3CSK 4下调这些mRNA。IL-1 β、TNF-α、CCL 20在来自龋齿的TcOB制剂中也上调6倍至30倍。我们的研究结果首次表明，OBs原位表达微生物模式识别受体，从而允许对革兰氏阳性菌和革兰氏阴性菌的不同反应，并表明龋齿中的促炎细胞因子和先天免疫反应可能来自TLR 4信号传导。
Odontoblasts (OBs) are cells lining the inner surface of the tooth. Their potential role in host defenses within the tooth is suggested by their production of antimicrobial beta-defensins, but their role needs confirmation. The present study sought to define the roles of human OBs in microbial recognition and innate host responses. Toll-like receptor 2 (TLR2) and TLR4, as well as CCR6, were immunolocalized in human OBs and their dentinal processes in situ. To examine OB function we used organotypic tooth crown cultures to maintain human OBs within their dentin scaffold. Cells in the OB layer of cultured and non-cultured crown preparations expressed mRNA for several markers of innate immunity including chemokine CCL20, chemokine receptor CCR6, TLR2, TLR4 and the OB marker dentin sialophosphoprotein (DSPP). Expression of human beta-defensin 1 (hBD1), hBD2, hBD3, interleukin-8 (IL-8), and CCL20 increased with time in culture. Tooth crown odontoblast (TcOB) cultures were stimulated with agonist that was specific for TLR2 (Pam3CSK4) or TLR4 [Escherichia coli lipopolysaccharide (LPS)]. Nuclear factor-kappa B assays confirmed the TLR2 activity of Pam3CSK4 and the TLR4 activity of LPS. LPS up-regulated IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), CCL20, hBD2, IL-8, TLR2 and TLR4; however, Pam3CSK4 down-regulated these mRNAs. IL-1 beta, TNF-alpha, CCL20 were also up-regulated from six-fold to 30-fold in TcOB preparations from decayed teeth. Our results show for the first time that OBs express microbial pattern recognition receptors in situ, thus allowing differential responses to gram-positive and gram-negative bacteria, and suggest that pro-inflammatory cytokines and innate immune responses in decayed teeth may result from TLR4 signaling.