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J Cell Physiol ; 215(1): 15-26, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18189229

ABSTRACT

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/ERK1/2, 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.


Subject(s)
Gene Expression Regulation/drug effects , Immunologic Factors/pharmacology , Interleukin-2/genetics , Protein Kinase C/metabolism , Reishi/immunology , Signal Transduction/drug effects , T-Lymphocytes/drug effects , CD3 Complex/metabolism , Calcium Signaling/drug effects , Cells, Cultured , Fungal Proteins/immunology , Fungal Proteins/pharmacology , Humans , Immunologic Factors/immunology , Interleukin-2/metabolism , Isoenzymes/metabolism , Jurkat Cells , Lymphocyte Activation/drug effects , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Reactive Oxygen Species/metabolism , Receptors, Antigen, T-Cell/metabolism , Recombinant Proteins/pharmacology , Reishi/chemistry , T-Lymphocytes/enzymology , T-Lymphocytes/metabolism , Time Factors , Type C Phospholipases/metabolism , src-Family Kinases/metabolism
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