Ling Zhi Immuno-Modulation Protein, LZ-8 Induction of Interleukin-1 Expression in Human Monocytes via Pertussis Toxin-Sensitive G Protein-Mediated Protein Kinase Pathway

Abstract

＂Ganoderma lucidum＂ (G. lucidum) (a medicinal fungus) has been known to enhance a variety of immune functions in humans and animals for centuries. An immunomodulatory protein, Ling Zhi-8 (LZ-8), is isolated from G. lucidum and exhibits potent mitogenic effects upon human immune cells. However, LZ-8-mediated signal transductions in the regulation of interleukin-1 (IL-1) gene expression within human monocytes has not been less well examined. In this study, we expressed the recombinant LZ-8 protein (rLZ) via Pichia pastoris protein expression system. We investigated the effect of rLZ on induction of IL-1 expression in human monocyte-like THP-1cells. We found that rLZ induced pro-interleukin 1 (proIL-1, a precursor of IL-1) and IL-1 protein expression in human monocytes THP-1 in time- and dose-dependent manners. We found that rLZ induced IL-1 gene expression via a pertussis toxin (PTX)-sensitive G protein-couple receptor (GPCR), phospholipase C (PLC) and various protein kinases-dependent pathways in THP-1 cells. In essence, we have established the nature of rLZ-mediated signaltransduction pathways, such as GPCR, PTK/ PI-3K/ PLC, PTK/ PLC/ PKCα/ JNK, and PTK/ PLC/ PKCδ/ θ/ ERK1/2, in the regulation of IL-1 gene expression in THP-1 cells. Our current results of the analysis of rLZ-mediated signal transduction in monocyte-like cells could provide a potential explanation and application of rLZ as a pharmacological immuno-modulating agent.