Do post-transcriptional mechanisms participate in induction of C-reactive protein and serum amyloid A by IL-6 and IL-1?
Do post-transcriptional mechanisms participate in induction of C-reactive protein and serum amyloid A by IL-6 and IL-1?
复制标题
转录后机制是否参与 IL-6 和 IL-1 诱导 C 反应蛋白和血清淀粉样蛋白 A 的过程？
DOI：
10.1111/j.1749-6632.1995.tb32318.x
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发表时间：
1995
影响因子：
5.2
通讯作者：
Samols,D
中科院分区：
文献类型：
--
作者：
Kushner,I;Jiang,SL;Zhang,D;Lozanski,G;Samols,D
两种主要的人类急性期蛋白是C反应蛋白（CRP）和血清淀粉样蛋白A（SAA）。在炎症刺激后，两者的浓度都显示出快速和显著的增加，由于肝细胞合成增加，在一些严重发炎的个体中达到的水平比基线高几千倍。此外，编码这些蛋白质的基因在它们对细胞因子的反应方面是相似的。在所研究的大多数模型系统中，这两种基因都是由白细胞介素（IL-6）诱导的，并且已经显示将IL-1添加到IL-6中对每种基因都具有协同作用。我们实验室的研究已经显示，这两种基因都需要IL-6和IL-1的组合以在Hep 3B细胞中实现最大应答，而在NPLC/PRF/S细胞中单独的IL-6就足够了。先前的研究已经清楚地表明转录在CRP和SAA的诱导中起主要作用。7-9此外，然而，转录后调控的可能性已提高了这两种蛋白质。使用转染到Hep 3B细胞中的CRP-CAT构建体研究IL-6和IL-1对CRP诱导的影响，显示这些构建体的主要诱导物是IL-6;发现IL-1作用在TATA盒下游序列的水平上发挥，包括5 '非翻译区（UTR）的前15个核苷酸。作者得出结论，IL-1的作用必须在转录后水平发挥，可能在翻译水平。
The two major human acute phase proteins are C-reactive protein (CRP) and serum amyloid A (SAA). Both display rapid and marked increases in concentration following inflammatory stimuli, levels several thousand-fold greater than baseline being achieved in some severely inflamed individuals as a result of increased synthesis in hepatoqtes. In addition, the genes encoding these proteins are similar in their response to cytokines. Both are induced by interleukind (IL-6) in most model systems studied,-5 and addition of IL-1 to IL-6 has been shown to have a synergistic effect on each Studies in our laboratory have shown that both genes required the combination of IL-6 and IL-1 to achieve maximal response in Hep 3B cells while IL-6 alone was sufficient in NPLC/PRF/S cells. Previous studies have clearly indicated that transcription plays a major role in induction of both CRP and SAA. 7-9 In addition, however, the possibility of posttranscriptional regulation has been raised for both proteins. Studies of the effects of IL-6 and IL-1 on CRP inductionY5 employing CRP-CAT constructs transfected into Hep 3B cells, showed the major inducer of these constructs to be IL-6; the IL-1 effect was found to be exerted at the level of sequences downstream to the TATA box, including the first 15 nucleotides of the 5'untranslated region (UTR). The authors concluded that the effect of IL-1 must be exerted at a post-transcriptional level, probably at the level of translation.