INNATE HOST DEFENSE AND ORAL EPITHELIAL CELL FATE

肿瘤坏死因子（TNF）和TNF受体（TNFR）家族在细胞发育和炎症过程中发挥重要作用，但它们如何调节口腔炎症反应和伤口愈合却知之甚少。我们将研究CD40， CD95和其他TNFR成员如何调节牙龈上皮细胞（gec）的命运。对于为什么儿童总体上对牙周病有抵抗力，以及在发生早发性牙周炎和口腔相关组织破坏的个体中抵抗力被破坏的机制知之甚少。该项目不仅将研究gec的命运如何在正常情况下受到调节，还将研究口腔细菌如何影响gec的生长或死亡。这些研究将有助于了解口腔病原体初始入侵的耐药或易感性的分子基础。我们的具体目的是：1)验证CD40或CD95调节TNFR家族成员在gec上的表达，从而使其易发生凋亡的假设。Fas单抗、CD40单抗、可溶性TNF- α或TRAIL诱导活化的gec凋亡的能力将被评估。我们将测试gec是否表达CD40L、FasL、TRAIL和tnf - α，特别是Fas结扎是否会影响牙龈粘膜的死亡或炎症反应；2)验证gec中CD40和Fas受体调控死亡通路相关基因的假说。CD40在gec中诱导的死亡途径相关基因将被深入评估在调节上皮细胞命运中的可能作用；3)验证口腔细菌调节牙龈上皮细胞和树突状细胞命运的假说。gec或CD1+ dc将暴露于浮游细菌或牙周病牙龈卟啉单胞菌（Pg）的生物膜和早期菌斑细菌。戈登氏链球菌（Sg）。比较浮游Pg或Sg或生物膜诱导趋化因子受体、TNF/TNFR家族成员及细胞命运基因的差异。进一步了解上皮细胞和树突状细胞的细胞死亡过程也可能导致对牙周组织中骨形成、再生和伤口愈合如何被调节的新见解。

The tumor necrosis factor (TNF) and TNF receptor (TNFR) families play essential roles in regulating the role of cells during development and inflammatory processes, yet relatively little is known about how they regulate inflammatory responses and wound healing in the oral cavity. We will examine how CD40, CD95 and other TNFR members regulate the fate of gingival epithelial cells (GECs). Very little is known about why children by-in-large re resistant to periodontal disease and what resistance mechanisms break down in individuals who develop early onset periodontitis and the associated tissue destruction in the oral cavity. This project will investigate not only how the fate of GECs is normally regulated but also how oral bacteria influence the growth or death of GECs. These studies will contribute to the understanding of the molecular basis of resistance or susceptibility to initial invasion by oral cavity pathogens. Our specific Aims are: 1) To test the hypothesis that CD40 or CD95 regulate the expression of TNFR family members on GECs, thereby making them susceptible to apoptosis. The ability of Fas mAB, CD40 mAb, soluble TNF- alpha or TRAIL to induce apoptosis of activated GECs will be evaluated. We will test if GECs express CD40L, FasL, TRAIL and TNF-alpha and in particular if Fas ligation may influence death or inflammatory responses in the gingival mucosa; 2) To test the hypothesis that death pathway-associated genes are regulated by CD40 and Fas receptors in GECs. The set of death pathway-associated genes induced in GECs by CD40 will be evaluated in depth for possible roles in regulating epithelial cell fate; 3) To tet the hypothesis that oral bacteria regulate gingival epithelial cell fate and dendritic cell fate. GECs or CD1+ DCs will be exposed to planktonic bacteria or biofilms of periodontopathic Porphyromonas gingivalis (Pg), and an early plaque bacterium. Streptococcus gordonii (Sg). Induction by planktonic Pg or Sg or biofilms of chemokine receptor, TNF/TNFR family members and cell fate genes will be compared. Further understanding of cell death processes in epithelial and dendritic cells could also lead to new insights into how bone formation, regeneration and wound healing in the periodontium are regulated.