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

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.

Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum

“…Collectively, this polysaccharide-dependent expression of cytokines and Ig employed signaling through the activation of MAPKs and NF-κB [65]. In addition, an immunomodulatory protein, purified from G. lucidum, stimulated the production of IL-1β, IL-2, TNF-α and IFN-γ by human peripheral blood lymphocytes [66], and modulated protein tyrosine kinase (PTK) and protein kinase C (PKC) signaling to produce IL-2 in human T cells [67]. Interestingly, only one study describes an induction of the immune response by G. lucidum triterpene, ganoderic acid Me, as demonstrated by the increased expression of IL-2 and IFN-γ in mice [68].…”

Ling Zhi-8 reduces lung cancer mobility and metastasis through disruption of focal adhesion and induction of MDM2-mediated Slug degradation

“…The LZ-8 expression plasmid and the purification of rLZ-8 protein were performed as previously described [34].…”

A novel adjuvant Ling Zhi-8 for cancer DNA vaccines

“…23 In addition, LZ-8 can work as a mitogen to activate T cells. 24 Jeurink et al reported that protein extracts of G. lucidum contain immunomodulating activity by acting directly on monocytes, 25 implying that proteins including LZ-8 in G. lucidum may stimulate myeloid cells. However, many other immunoregulatory functions of LZ-8 remain to be explored.…”