Ushio S, Namba M, Okura T, Hattori K, Nukada Y, Akita K, Tanabe F, Konishi K, Micallef M, Fujii M, Torigoe K, Tanimoto T, Fukuda S, Ikeda M, Okamura H, Kurimoto M
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
J Immunol. 1996 Jun 1;156(11):4274-9.
We have recently reported that a novel molecule, murine IFN-gamma-inducing factor (IGIF) produced by mouse liver cells, possesses potent biologic activities, including the induction of IFN-gamma production by spleen cells and the enhancement of NK cell cytotoxicity. In this paper, we report on the isolation of human IGIF cDNA clones from normal human liver cDNA libraries using murine IGIF cDNA as a probe. The amino acid sequence deduced from the human cDNA clones indicated a 193-amino acid precursor peptide and revealed 65% homology with that of murine IGIF. The amino acid sequence of IGIF also included an IL-1 signature-like sequence. Subsequently, the cloned cDNA was expressed in Escherichia coli, and preliminary studies on the biologic activities of the recombinant protein were performed. The recombinant human IGIF induced IFN-gamma production by mitogen-stimulated PBMC and enhanced NK cell cytotoxicity, in a manner similar to murine IGIF. In addition, recombinant human IGIF also augmented granulocyte-macrophage-CSF production and decreased IL-10 production, but had no effect on IL-4 production by Con A-stimulated PBMC. Based on these pleiotropic effects of IGIF, we propose that this novel cytokine be designated as IL-18.
我们最近报道，一种由小鼠肝细胞产生的新型分子——小鼠γ干扰素诱导因子（IGIF），具有强大的生物学活性，包括诱导脾细胞产生γ干扰素以及增强自然杀伤（NK）细胞的细胞毒性。在本文中，我们报道了以小鼠IGIF cDNA为探针，从正常人肝脏cDNA文库中分离出人IGIF cDNA克隆的过程。从人cDNA克隆推导的氨基酸序列显示为一个193个氨基酸的前体肽，与小鼠IGIF的氨基酸序列有65%的同源性。IGIF的氨基酸序列还包含一个白细胞介素-1（IL-1）特征样序列。随后，将克隆的cDNA在大肠杆菌中表达，并对重组蛋白的生物学活性进行了初步研究。重组人IGIF以类似于小鼠IGIF的方式，诱导丝裂原刺激的外周血单个核细胞（PBMC）产生γ干扰素，并增强NK细胞的细胞毒性。此外，重组人IGIF还增加了粒细胞-巨噬细胞集落刺激因子（GM-CSF）的产生，减少了IL-10的产生，但对刀豆蛋白A刺激的PBMC产生IL-4没有影响。基于IGIF的这些多效性作用，我们建议将这种新型细胞因子命名为IL-18。
