Reishi immuno-modulation protein induces interleukin-2 expression via protein kinase-dependent signaling pathways within human T cells
Reishi immuno-modulation protein induces interleukin-2 expression via protein kinase-dependent signaling pathways within human T cells
复制标题
DOI：
10.1002/jcp.21144
复制
发表时间：
2008-04-01
影响因子：
5.6
通讯作者：
Huang, Ching-Tsan
中科院分区：
文献类型：
--
作者：
Hsu, Hsien-Yeh;Hua, Kuo-Feng;Huang, Ching-Tsan
灵芝是一种药用真菌，被认为具有增强人体免疫力的多种功能。灵芝-8（LZ-8）是一种免疫调节蛋白，从灵芝中分离得到。灵芝对人外周血淋巴细胞（PBL）有较强的促有丝分裂作用。然而，LZ-8介导的信号转导在调节白细胞介素-2（IL-2）基因在人T细胞内的表达在很大程度上是未知的。本研究克隆了G. lucidum中表达，并通过酵母毕赤酵母蛋白表达系统表达重组LZ-8蛋白（rLZ-8）。我们发现rLZ-8通过Src家族蛋白酪氨酸激酶（PTK）、活性氧（ROS）和人原代T细胞和培养的Jurkat T细胞内的差异蛋白激酶依赖性途径诱导IL-2基因表达。从本质上讲，我们已经建立了rLZ-8介导的信号转导途径，如PTK/蛋白激酶C（PKC）/ROS，PTK/PLC/PKCalpha/ERK 1/2和PTK/PLC/PKCalpha/p38途径在调节人T细胞内IL-2基因表达中的性质。我们目前的结果分析rLZ-8介导的信号转导在T细胞可能提供了一个潜在的应用rLZ-8作为一个药理免疫调节剂。
Ganoderma lucidum, a medicinal fungus is thought to possess and enhance a variety of human immune functions. An immuno-modulatory protein, Ling Zhi-8 (LZ-8) isolated from G. lucidum exhibited potent mitogenic effects upon human peripheral blood lymphocytes (PBL). However, LZ-8-mediated signal transduction in the regulation of interleukin-2 (IL-2) gene expression within human T cells is largely unknown. Here we cloned the LZ-8 gene of G. lucidum, and expressed the recombinant LZ-8 protein (rLZ-8) by means of a yeast Pichia pastoris protein expression system. We found that rLZ-8 induces IL-2 gene expression via the Src-family protein tyrosine kinase (PTK), via reactive oxygen species (ROS), and differential protein kinase-dependent pathways within human primary T cells and cultured Jurkat T cells. In essence, we have established the nature of the rLZ-8-mediated signal-transduction pathways, such as PTK/protein kinase C (PKC)/ROS, PTK/PLC/PKCalpha/ERK 1/2, and PTK/PLC/PKCalpha/p38 pathways in the regulation of IL-2 gene expression within human T cells. Our current results of analyzing rLZ-8-mediated signal transduction in T cells might provide a potential application for rLZ-8 as a pharmacological immune-modulating agent.