Ganter U, Arcone R, Toniatti C, Morrone G, Ciliberto G
Dipartimento di Biochimica e Biotecnologie Mediche, Universita di Napoli, Italy.
EMBO J. 1989 Dec 1;8(12):3773-9. doi: 10.1002/j.1460-2075.1989.tb08554.x.
Human C-reactive protein (CRP) is the major acute phase reactant during acute inflammation. The human CRP promoter is expressed in an inducible and cell-specific manner when linked to the bacterial CAT gene and transfected into human hepatoma cell cultures. In this paper we analyze the effect of several recombinant cytokines or CRP promoter inducibility in human Hep3B cells. When cytokines are tested singly the major inducer of CRP-CAT fusions is interleukin-6 (IL-6). Maximal CAT gene expression, however, is only achieved when both interleukin-1 beta (IL-1 beta) and IL-6 are present. The response to the two cytokines is cooperative. Cooperativity is maintained when the CRP promoter is linked to a different coding region, that of the bacterial neomycin phosphotransferase II gene. With a series of 5' and 3' deletions we show the existence of two distinct and independent regions responsive to IL-6 and located upstream to the TATA box. The IL-1 effect is exerted at the level of downstream sequences that are probably important for optimal mRNA translatability or nuclear-cytoplasmic transport. Inducibility is not influenced by the activation of protein kinases C or A and does not require new protein synthesis.
人C反应蛋白（CRP）是急性炎症期间的主要急性期反应物。当与细菌氯霉素乙酰转移酶（CAT）基因连接并转染到人肝癌细胞培养物中时，人CRP启动子以诱导性和细胞特异性方式表达。在本文中，我们分析了几种重组细胞因子对人Hep3B细胞中CRP启动子诱导性的影响。当单独检测细胞因子时，CRP-CAT融合物的主要诱导剂是白细胞介素-6（IL-6）。然而，只有当白细胞介素-1β（IL-1β）和IL-6都存在时，才能实现最大的CAT基因表达。对这两种细胞因子的反应是协同的。当CRP启动子与细菌新霉素磷酸转移酶II基因的不同编码区连接时，协同作用得以维持。通过一系列5'和3'缺失，我们发现存在两个不同且独立的区域，它们对IL-6有反应，且位于TATA框上游。IL-1的作用在下游序列水平发挥，这些序列可能对最佳mRNA可翻译性或核质运输很重要。诱导性不受蛋白激酶C或A激活的影响，也不需要新的蛋白质合成。
