Inhibition of interleukin-1-induced effects in synoviocytes transduced with the human IL-1 receptor antagonist cDNA using an adenoviral vector.
Inhibition of interleukin-1-induced effects in synoviocytes transduced with the human IL-1 receptor antagonist cDNA using an adenoviral vector.
复制标题
使用腺病毒载体转导人 IL-1 受体拮抗剂 cDNA 来抑制滑膜细胞中白细胞介素 1 诱导的作用。
DOI：
10.1089/hum.1995.6.3-307
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Davidson,BL
中科院分区：
文献类型：
--
作者：
Roessler,BJ;Hartman,JW;Vallance,DK;Latta,JM;Janich,SL;Davidson,BL
在本报告中，我们提供的数据表明，含有人白细胞介素1受体拮抗剂蛋白（IL-1ra）cDNA的重组腺病毒载体（Ad.RSVIL-1ra）可以在体外和体内对滑膜细胞进行遗传修饰。通过组织培养上清液的 ELISA 检测，感染 Ad.RSVIL-1ra 的人滑膜细胞在体外表达并分泌高水平的人 IL-1ra。接受关节内注射Ad.RSVIL-1ra的新西兰白兔在滑膜细胞中表达转基因IL-1ra，并且在感染后至少4周内检测到分泌。此外，转基因IL-1ra的生物活性通过其体外抑制IL-1诱导的前列腺素E2(PGE2)合成和体内IL-1诱导的糖胺聚糖(GAG)降解的能力得到证明。这些数据表明重组腺病毒载体可以介导抗炎蛋白的关节内表达，并且可能是递送治疗相关蛋白用于滑膜炎症的区域治疗的合理方法。
In this report, we present data showing that a recombinant adenoviral vector (Ad.RSVIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist protein (IL-1ra) can genetically modify synoviocytes bothin vitroandin vivo. Human synoviocytes infected with Ad.RSVIL-1ra in vitroexpressed and secreted high levels of human IL-1ra that were detected by ELISA of tissue culture supernatants. New Zealand White rabbits that received intra-articular injections of Ad.RSVIL-1raexpressed transgenic IL-1ra in synoviocytes, and secretion was detected for at least 4 weeks post-infection. Further, biological activity of the transgenic IL-1ra was demonstrated by its ability to inhibit IL-1-induced prostaglandin E2(PGE2) synthesisin vitroand IL-1-induced glycosaminoglycan (GAG) degradationin vivo. These data demonstrate that recombinant adenoviral vectors can mediate the intra-articular expression of anti-inflammatory proteins and may be a reasonable method to deliver therapeutically relevant proteins for the regional treatment of synovial inflammation.