Jambou R C, Snouwaert J N, Bishop G A, Stebbins J R, Frelinger J A, Fowlkes D M
Department of Pathology, University of North Carolina, Chapel Hill 27599.
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9426-30. doi: 10.1073/pnas.85.24.9426.
Hepatocyte-stimulating factor, interferon-beta 2, B-cell stimulation factor 2, and hybridoma/plasmacytoma growth factor are identical proteins presently referred to as interleukin 6 (IL-6). Through the use of synthetic oligonucleotide technology, we have constructed a biologically active recombinant IL-6 (rIL-6) gene based on the sequence of a human IL-6 cDNA. The synthetic gene encodes a cysteine-free, bioengineered rIL-6 protein that is expressed at high levels in Escherichia coli as a tripartite fusion protein. Cleavage of the fusion protein with collagenase releases a 23-kDa rIL-6 protein that can be easily purified to homogeneity. We show that the rIL-6 protein displays a range of biological activities similar to those of natural human IL-6, as demonstrated by its ability to (i) protect cells from viral infection, (ii) stimulate the synthesis of fibrinogen in rat FAZA 967 cells, and (iii) induce the terminal differentiation of B cells, resulting in elevated secretion of immunoglobulin.
肝细胞刺激因子、β-干扰素2、B细胞刺激因子2以及杂交瘤/浆细胞瘤生长因子是目前被称为白细胞介素6（IL-6）的同一类蛋白质。通过使用合成寡核苷酸技术，我们基于人IL-6 cDNA的序列构建了一个具有生物活性的重组IL-6（rIL-6）基因。该合成基因编码一种无半胱氨酸的、经过生物工程改造的rIL-6蛋白，它在大肠杆菌中作为一种三方融合蛋白高水平表达。用胶原酶切割融合蛋白可释放出一种23 kDa的rIL-6蛋白，该蛋白可轻松纯化至同质。我们表明，rIL-6蛋白表现出一系列与天然人IL-6相似的生物活性，这通过其以下能力得以证明：（i）保护细胞免受病毒感染；（ii）刺激大鼠FAZA 967细胞中纤维蛋白原的合成；（iii）诱导B细胞的终末分化，导致免疫球蛋白分泌增加。
