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肝细胞生长因子和视黄酸对大鼠肝癌细胞中1型和2型急性期蛋白的合成具有相反的作用。

Hepatocyte growth factor and retinoic acid exert opposite effects on synthesis of type 1 and type 2 acute phase proteins in rat hepatoma cells.

作者信息

Koj A, Guzdek A, Nakamura T, Kordula T

机构信息

Institute of Molecular Biology, Jagiellonian University, Krakow, Poland.

出版信息

Int J Biochem Cell Biol. 1995 Jan;27(1):39-46. doi: 10.1016/1357-2725(94)00058-1.

DOI:10.1016/1357-2725(94)00058-1
PMID:7538894
Abstract

Rat hepatoma cells H-35 cultured in serum-free medium were exposed to interleukin-6 (IL-6), interleukin-1 (IL-1), hepatocyte growth factor (HGF), retinoic acid (RA), or a mixture of these factors. Production of acute phase proteins, responding to IL-6 alone (type 2) or to the mixture of IL-6 and IL-1, was assessed by electroimmunoassay and the corresponding mRNAs were compared by Northern blot analysis. HGF enhanced IL-6-induced synthesis of alpha-2-macroglobulin but reduced synthesis of C3 complement and alpha-1-acid glycoprotein. Retinoic acid reduced the response to IL-6 of alpha-2-macroglobulin but enhanced that of alpha-1-acid glycoprotein and especially of C3 complement. In general, changes in protein secretion were correlated with the contents of their corresponding cellular mRNAs. These results indicate that hepatocyte growth factor can enhance basal or IL-6-induced gene expression of type 2 and reduce the expression of type 1 acute phase proteins, whereas the action of retinoic acid is opposite. The modulation of acute phase response by HGF and RA likely involves transcriptional factors and regulatory sequences in the genes coding for these two types of acute phase proteins.

摘要

将无血清培养基中培养的大鼠肝癌细胞H-35暴露于白细胞介素-6(IL-6)、白细胞介素-1(IL-1)、肝细胞生长因子(HGF)、视黄酸(RA)或这些因子的混合物中。通过电免疫测定法评估仅对IL-6(2型)或IL-6与IL-1混合物作出反应的急性期蛋白的产生,并通过Northern印迹分析比较相应的mRNA。HGF增强了IL-6诱导的α-2-巨球蛋白的合成,但降低了C3补体和α-1-酸性糖蛋白的合成。视黄酸降低了α-2-巨球蛋白对IL-6的反应,但增强了α-1-酸性糖蛋白尤其是C3补体的反应。一般来说,蛋白质分泌的变化与其相应细胞mRNA的含量相关。这些结果表明,肝细胞生长因子可增强2型急性期蛋白的基础表达或IL-6诱导的基因表达,并降低1型急性期蛋白的表达,而视黄酸的作用则相反。HGF和RA对急性期反应的调节可能涉及这两种类型急性期蛋白编码基因中的转录因子和调控序列。

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