Reishi immuno-modulation protein induces interleukin-2 expression via protein kinase-dependent signaling pathways within human T cells

J Cell Physiol. 2008 Apr;215(1):15-26. doi: 10.1002/jcp.21144.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • CD3 Complex
  • Fungal Proteins
  • Immunologic Factors
  • Interleukin-2
  • Isoenzymes
  • Reactive Oxygen Species
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • src-Family Kinases
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases