Development of novel therapy for TMJ arthritis by Gene transfer using with sonoporation combined with microbubble-based ultrasound contrast agent

外源性IL-1受体拮抗剂(IL-1ra)可有效减轻IL-1介导的炎症反应。本研究采用声波法将含有IL-1ra基因的真核表达载体导入滑膜细胞，观察IL-1ra基因导入对内毒素诱导的滑膜细胞炎症反应的影响。IL-1ra基因转染的滑膜细胞产生细胞外IL-1ra，与脂多糖共同培养48h后，IL-1ra的水平显著升高。有趣的是，脂多糖可促进IL-1ra转基因细胞培养上清液中IL-1β的释放，而60h后PGE_2的释放明显减少，提示IL-1ra基因对滑膜细胞的炎症反应具有重要的调节作用，提示IL-1ra基因的干预是控制关节炎炎症的有效方法。

Administration of exogenous IL-1 receptor antagonist (IL-1ra) is effective in reducing the inflammatory reactions mediated by IL-1. In the present study, we transfected with a plasmid containing IL-1ra gene into synovial cells by the sonoporation method, and investigated the effect of IL-1ra gene transfection on inflammatory reactions induced by lipopolysaccharide (LPS) in vitro. IL-1ra- transfected synovial cells produced the extracellular IL-lra, and its level increased remarkably when the cells were cultured with LPS for 48 h. Interestingly, treatment of LPS enhanced the release of IL-1β in the culture supernatant of IL-1ra-transfected cells, however, a significant decrease of PGE2 release was observed when the cells were cultured with LPS for 60 h. These results indicate that IL-1ra could play a valuable regulatory role in inflammatory reactions of synovial cells, suggesting that the administration of IL-1ra gene with sonoporation is a useful method for the control of inflammation in arthritis.