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细胞因子对小鼠血清淀粉样蛋白P基因表达的体外调控

Regulation of mouse serum amyloid P gene expression by cytokines in vitro.

作者信息

Zahedi K, Whitehead A S

机构信息

Department of Pediatrics, University of Cincinnati Medical School, OH.

出版信息

Biochim Biophys Acta. 1993 Mar 10;1176(1-2):162-8. doi: 10.1016/0167-4889(93)90192-r.

Abstract

Inflammation is accompanied by an increase in the plasma levels of a number of proteins collectively known as acute-phase reactants (APRs). Serum amyloid P component (SAP) is a major mouse APR: hepatic SAP mRNA and plasma SAP protein concentrations increase by up to 20-fold in mice undergoing an inflammatory response. In-vitro studies, using primary hepatocyte cultures, have previously shown that SAP mRNA and protein levels increase in response to stimulation with a variety of cytokines such as monocyte-conditioned medium (MCM), interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta). In this report, we have examined a mouse hepatoma cell line in which SAP gene regulation closely resembles that of primary hepatocytes. Accumulation of SAP mRNA in the +/+ Li mouse hepatoma cell line after stimulation with MCM, IL-1, IL-6 and the combination of IL-1 and IL-6 was demonstrated. This increase in the cellular content of SAP mRNA did not require new protein synthesis and was at least partially due to an increase in the transcription rate of the SAP gene.

摘要

炎症伴随着多种蛋白质的血浆水平升高,这些蛋白质统称为急性期反应物(APR)。血清淀粉样蛋白P成分(SAP)是主要的小鼠APR:在发生炎症反应的小鼠中,肝脏SAP mRNA和血浆SAP蛋白浓度可增加多达20倍。先前使用原代肝细胞培养物进行的体外研究表明,SAP mRNA和蛋白水平会因多种细胞因子(如单核细胞条件培养基(MCM)、白细胞介素1(IL-1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和转化生长因子β(TGF-β))的刺激而增加。在本报告中,我们研究了一种小鼠肝癌细胞系,其中SAP基因调控与原代肝细胞非常相似。在用MCM、IL-1、IL-6以及IL-1和IL-6的组合刺激后,在+/+ Li小鼠肝癌细胞系中证实了SAP mRNA的积累。SAP mRNA细胞含量的这种增加不需要新的蛋白质合成,并且至少部分是由于SAP基因转录速率的增加。

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