McLachlan Julia L, Sloan Alastair J, Smith Anthony J, Landini Gabriel, Cooper Paul R
Oral Biology, School of Dentistry, The University of Birmingham, Birmingham B4 6NN, United Kingdom.
Infect Immun. 2004 Jul;72(7):4102-8. doi: 10.1128/IAI.72.7.4102-4108.2004.
The molecular immune response of the pulpal tissue during chronic carious infection is poorly characterized. Our objective was to examine the expression of potential molecular mediators of pulpal inflammation, correlate their levels with disease severity, and determine the cellular localization of key molecules. Results indicated that there was significantly increased transcriptional activity in carious compared to healthy pulp, and the increase correlated positively with disease severity. Semiquantitative reverse transcriptase PCR analysis in 10 carious and 10 healthy pulpal tissue samples of the S100 family members S100A8, S100A9, S100A10, S100A12, and S100A13; the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-8, IL-6, and epithelial cell-derived neutrophil attractant 78 (ENA-78); and the structural protein collagen-1alpha indicated that all genes tested, with the exception of S100A10, were more abundantly expressed in carious teeth. In addition, we found that the closer the carious lesion front was to the pulpal chamber the higher the expression was for all genes except S100A10. Multiple-regression analysis identified a significant positive correlation between the expression levels of S100A8 and IL-1beta, ENA-78, and IL-6 and between collagen-1alpha and S100A8, TNF-alpha, IL-1beta, IL-8, IL-6, and ENA-78. Immunohistochemical studies in carious pulpal tissue indicated that S100A8 and the S100A8/S100A9 complex were predominantly expressed by infiltrating neutrophils. Gene expression analyses in immune system cells supported these findings and indicated that bacterial activation of neutrophils caused upregulation of S100A8, S100A9, and S100A13. This study highlights the complex nature of the molecular immune response that occurs during carious infection.
在慢性龋感染期间，牙髓组织的分子免疫反应特征尚不明确。我们的目的是研究牙髓炎症潜在分子介质的表达，将它们的水平与疾病严重程度相关联，并确定关键分子的细胞定位。结果表明，与健康牙髓相比，龋损牙髓中的转录活性显著增加，且这种增加与疾病严重程度呈正相关。对10个龋损牙髓组织样本和10个健康牙髓组织样本进行半定量逆转录聚合酶链反应分析，检测S100家族成员S100A8、S100A9、S100A10、S100A12和S100A13；细胞因子肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）、IL-8、IL-6和上皮细胞衍生的中性粒细胞趋化因子78（ENA-78）；以及结构蛋白胶原蛋白-1α，结果显示，除S100A10外，所有检测基因在龋损牙齿中表达更为丰富。此外，我们发现龋损病变前沿距离牙髓腔越近，除S100A10外的所有基因表达越高。多元回归分析确定S100A8与IL-1β、ENA-78和IL-6的表达水平之间以及胶原蛋白-1α与S100A8、TNF-α、IL-1β、IL-8、IL-6和ENA-78的表达水平之间存在显著正相关。龋损牙髓组织的免疫组织化学研究表明，S100A8和S100A8/S100A9复合物主要由浸润的中性粒细胞表达。免疫系统细胞中的基因表达分析支持了这些发现，并表明中性粒细胞的细菌激活导致S100A8、S100A9和S100A13上调。本研究突出了龋感染期间发生的分子免疫反应的复杂性。
