Reishi immuno-modulation protein induces interleukin-2 expression via protein kinase-dependent signaling pathways within human T cells.
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.
Hsu
Hsien-Yeh
HY
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan. rshseu@ntu.edu.tw
Hua
Kuo-Feng
KF
Wu
Wei-Chi
WC
Hsu
Jason
J
Weng
Shih-Ting
ST
Lin
Tsai-Leng
TL
Liu
Chun-Yi
CY
Hseu
Ruey-Shyang
RS
Huang
Ching-Tsan
CT
D017252:CD3 Complex / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D005656:Fungal Proteins / Q000276:immunology / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020940:Reishi / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D017252:CD3 Complex; D005656:Fungal Proteins; D007155:Immunologic Factors; D007376:Interleukin-2; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D019061:src-Family Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases