Regulation of inflammation and innate immunity by TLR agonists

细菌是牙周炎的常见原因，在牙周炎中，加速的牙槽骨吸收可能最终导致牙齿脱落。众所周知，细菌通过细胞壁成分与相应的Toll样受体(TLRs)结合而与宿主细胞相互作用。其中，脂多糖是TLR4的配体，是最明确的分子，是破骨细胞形成和骨吸收的有效诱导剂。另一方面，除了TLR4外，TLR2在前体细胞和分化的破骨细胞中都有显著表达，这增加了TLR2参与牙周炎相关性骨溶解的可能性。在本研究中，我们研究了TLR2的配体Pam3CSK4是否在体内引起骨吸收。结果表明，与脂多糖相比，Pam3CSK4诱导的牙槽骨吸收更严重，提示Pam3CSK4诱导的骨溶解反应从炎症到天然免疫的转变时间比内毒素延长。

Bacteria are a common cause of periodontitis, in which accelerated alveolar bone resorption may ultimately lead to tooth loss. It is well established that bacteria interact with host cells through components of their cell wall by binding to corresponding Toll-like receptors (TLRs). Among these, LPS, a ligand for TLR4, is the most clearly defined molecule as a potent inducer of osteoclastogenesis and bone resorption. On the other hand, the fact that TLR2, in addition to TLR4, was prominently expressed in both precursors and differentiated osteoclasts, raised the possibility that TLR2 is involved in periodontitis-associated osteolysis. In the present study, we studied whether Pam3CSK4, a ligand for TLR2, caused bone resorption in vivo. The results showed that Pam3CSK4 caused even severer alveolar bone resorption as compared to LPS, indicating that transition time from inflammation to innate immunity was prolonged in Pam3CSK4-induced osteolysis compared to that of LPS.