摘要：
Toll样受体(Toll like receptor,TLR)是先天免疫反应的模式识别受体,负责识别病原体、介导前炎症细胞因子的产生并启动免疫应答.IRAK家族是TLR的白细胞介素1受体(interleukin-1,IL1-R)信号通路中的重要分子,参与细胞内的信号网络控制和炎症反应,发挥正向或者负向的调节作用.该家庭共有4个成员:包括IRAK1、IRAK2、ITAKM(I-RAK3)和IRAK4,通过其激酶活性和接头分子的作用,介导一系列胞内的信号转导,最终导致前炎症学龄细胞因子等基因的表达.
摘要：
目的:研究乙型肝炎病毒(hepatitis B virus,HBV)重组腺病毒对HepG2细胞的IL-17R和接头蛋白Actl表达的影响,以及HBV对IL-17诱导NF-kB活化的影响.方法:采用实时荧光定量PCR(real-time PCR)检测HepG2细胞的IL-17、IL-17R和Actl的mRNA表达;蛋白免疫印迹法(Westem blot)检测IL-17R和Actl的蛋白表达；免疫荧光检测NF-kB核移位；ELISA检测上清的IL-17含量.结果:各组HepG2细胞培养上清液中均未检测到1L-17且亦未检测HepG2细胞有IL-17的mRNA表达；HBV重组腺病毒组的IL-17RmRNA和蛋白的表达明显低于相应浓度对照组(0.68±0.02 vs 0.89±0.03,0.33±0.06 vs0.81±0.01,0.12±0.01 vs 0.86±0.05,P＜0.05;蛋白:0.84±0.12 vs l.01±0.13,0.56±0.09vs l.01±0.08,0,24±0.08 vs 0.98±0.05),且呈剂量和时间依赖性.但HBV重组腺病毒组与对照组比较,对HepG2细胞接头蛋白Actl的mRNA和蛋白表达水平无明显影响；同时HBV重组腺病毒能抑制IL-17R诱导HepG2细胞的NF-kB活化,但HBV重组腺病毒与对照组比较,对接头蛋白Acti在mRNA和蛋白表达水平上影响无明显变化；同时HBV重组腺病毒能抑制IL- 17 R诱-导HepG2细胞的NF-kB活化,结论:HBV重组腺病毒可降低HepG2细胞的IL- 17R mRNA和蛋白的表达,抑制IL-17R诱导HepG2细胞的NF-kB活化,对HepG2细胞的IL-17R信号通路发挥抑制作用.
通讯机构：
[Xiao, Jianhua] U;Univ S China, Inst Pathogen Biol, Hengyang 421001, Hunan, Peoples R China.
关键词：
Schistosoma japonicum;eggshell protein gene;hammerhead ribozyme;in vitro cleavage;anti-reproduction
摘要：
Schistosoma japonicum (S. japonicum) is an extremely harmful pathogen, which infects humans and causes severe public health problems. To date, no effective therapeutic drugs for this pathogen are available. In this study, we designed and constructed three hammerhead ribozymes targeting the eggshell protein gene of S. japonicum (SjESG). The cleavage activities of these three ribozymes were determined using cleavage experiments. The in vitro cleavage results showed that among the three synthesized ribozymes (Rz1, Rz2 and Rz3), Rz1 and Rz3 cleaved their target RNAs effectively. However, Rz2 did not cleave its target RNA detectably. The putative therapeutic roles of these three ribozymes to inhibit the reproduction of S. japonicum in mice were studied in vivo. Compared with the negative controls, Rz1 and Rz3 treatments resulted in increased levels of IFN-γ but decreased levels of IL-4 in mice. Rz2 affected levels of IFN-γ and IL-4 to degrees similar with those caused by the vector controls. In addition, Rz1 and Rz3 reduced the amounts of adult worms and eggs in the livers of mice more extensively than Rz2 and the vector controls. Altogether, these results suggest a correlation between the in vitro cleavage abilities of Rz1 and Rz3 and their roles in reproduction inhibition of S. japonicum.
通讯机构：
[Li, Xiaoxia] C;Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, 9500 Euclid Ave,NE20, Cleveland, OH 44195 USA.
关键词：
Cytokines
摘要：
Interleukin-1 receptor-associated kinase 2 (IRAK2) has been shown to be essential for lipopolysaccharide (LPS)-mediated posttranscriptional control of cytokine and chemokine production. In this study, we investigated the role of IRAK2 kinase activity in LPS-mediated posttranscriptional control by reconstituting IRAK2-deficient macrophages with either wild-type or kinase-inactive IRAK2. Compared with wild-type IRAK2 (IRAK2-WT) macrophages, kinase-inactive IRAK2 (IRAK2-KD) macrophages show reduced cytokine and chemokine mRNA stability and translation in response to LPS. Further, LPS-treated IRAK2-KD macrophages also show reduced activation of MKK3/6, MNK1, and eIF4E and attenuated toll-like receptor 4-induced tristetraprolin modification and stabilization. Taken together, these results suggest that the kinase activity of IRAK2 is required for the optimal activation of mitogen-activated protein kinase signaling, which regulates cytokine and chemokine production at posttranscriptional levels.
