Pesu Marko, Muul Linda, Kanno Yuka, O'Shea John J
MIIB-NIAMS-NIH, Bldg 10, Rm 9N262, 10 Center Dr, Bethesda, MD 20892, USA.
Blood. 2006 Aug 1;108(3):983-5. doi: 10.1182/blood-2005-09-3824. Epub 2006 Apr 20.
Interleukin 12 (IL-12) is a major inducer of interferon gamma (IFN-gamma) and the principal mediator of T helper 1 (Th1) differentiation. To identify IL-12-regulated genes, which might contribute to Th1 differentiation and IFNG regulation, we employed microarray analysis. Surprisingly, a ubiquitously expressed proprotein convertase (PC), furin, was one of the most consistently IL-12-induced genes in T cells, and among PCs was the only one regulated by this cytokine. Furin was preferentially expressed in differentiated Th1 cells in a Stat4-dependent manner. Expression of furin enhanced IFN-gamma secretion, whereas inhibition of furin interfered with IFN-gamma production. Thus, we conclude that IL-12 induction of furin might represent a new aspect of IFN-gamma regulation and control of Th1 differentiation.
白细胞介素12(IL-12)是γ干扰素(IFN-γ)的主要诱导剂,也是辅助性T细胞1(Th1)分化的主要介导因子。为了鉴定可能有助于Th1分化和IFNG调控的IL-12调控基因,我们采用了微阵列分析。令人惊讶的是,一种广泛表达的前蛋白转化酶(PC)——弗林蛋白酶,是T细胞中最稳定受IL-12诱导的基因之一,并且在所有PC中是唯一受这种细胞因子调控的。弗林蛋白酶以Stat4依赖的方式在分化的Th1细胞中优先表达。弗林蛋白酶的表达增强了IFN-γ的分泌,而抑制弗林蛋白酶则干扰了IFN-γ的产生。因此,我们得出结论,IL-12诱导弗林蛋白酶可能代表了IFN-γ调控和Th1分化控制的一个新方面。