Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1β are differentially regulated in human blood mononuclear cells and mouse spleen cells
Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1β are differentially regulated in human blood mononuclear cells and mouse spleen cells
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DOI：
10.1073/pnas.96.5.2256
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Dinarello, CA
中科院分区：
文献类型：
--
作者：
Puren, AJ;Fantuzzi, G;Dinarello, CA
白细胞介素(IL)-18，以前被称为干扰素γ (ifn - γ)诱导因子，在生物学和结构上与IL-1 β相关。在人外周血单核细胞（PBMCs）和人全血中比较了IL-18和IL-1 β的基因表达、合成和加工。与IL-1 β类似，IL-18的前体需要caspase 1处理。在PBMCs中，成熟而非前体IL-18诱导ifn - γ；在内毒素刺激的全人血液中，抑制caspase 1通过不依赖于IL-1 β的机制减少ifn - γ的产生。与IL-1 β的前体不同，IL-18的前体在pbmc和来自健康人类供者的新鲜全血中组成性表达。内毒素刺激PBMCs的Western印迹显示，上清液中加工过的IL-1 β通过caspase i依赖途径存在。然而，在相同的上清液中，只发现未处理的前体IL-18。出乎意料的是，在新鲜获得的pbmc中发现了前体IL-18，健康供者的全血中存在组成性IL-18基因表达，而组成性IL-1 β基因表达不存在。与人PBMCs类似，小鼠脾细胞也组成性地含有IL-18预形成的前体并表达稳态IL-18 mRNA，但在这些相同的制剂中没有IL-1 β蛋白和IL-1 β的自发基因表达。我们得出结论，尽管IL-18和IL-1 β可能是同一家族的成员，但这两种细胞因子的构成基因表达、合成和加工是不同的。
Interleukin (IL)-18, formerly called interferon gamma (IFN-gamma)-inducing factor, is biologically and structurally related to IL-1 beta. A comparison of gene expression, synthesis, and processing of IL-18 with that of IL-1 beta was made in human peripheral blood mononuclear cells (PBMCs) and in human whole blood. Similar to IL-1 beta, the precursor for IL-18 requires processing by caspase 1. In PBMCs, mature but not precursor IL-18 induces IFN-gamma; in whole human blood stimulated with endotoxin, inhibition of caspase 1 reduces IFN-gamma production by an IL-1 beta-independent mechanism. Unlike the precursor for IL-1 beta, precursor for IL-18 was expressed constitutively in PBMCs and in fresh whole blood from healthy human donors. Western blotting of endotoxin-stimulated PBMCs revealed processed IL-1 beta in the supernatants via an caspase I-dependent pathway. However, in the same supernatants, only unprocessed precursor IL-18 was found. Unexpectedly, precursor IL-18 was found in freshly obtained PBMCs and constitutive IL-18 gene expression was present in whole blood of healthy donors, whereas constitutive IL-1 beta gene expression is absent. Similar to human PBMCs, mouse spleen cells also constitutively contained the preformed precursor for IL-18 and expressed steady-state IL-18 mRNA, but there was no IL-1 beta protein and no spontaneous gene expression for IL-1 beta in these same preparations. We conclude that although IL-18 and IL-1 beta are likely members of the same family, constitutive gene expression, synthesis, and processing are different for the two cytokines.