4-Hydroxy-17-methylincisterol fromAgaricus blazeiDecreased Cytokine Production and Cell Proliferation in Human Peripheral Blood Mononuclear Cells via Inhibition of NF-AT and NF-κB Activation

Abstract

Agaricus blazeiMurill is an edible and medicinal mushroom. In the previous study, we have proved that extracts ofA. blazeiinhibit human peripheral blood mononuclear cell (PBMC) proliferation activated with phytohemagglutinin (PHA). Currently, we purified 4-hydroxy-17-methylincisterol (4-HM; C21H33O3) fromA. blazeiinvestigated its regulatory effects on cytokine productions and cell proliferation of PBMC induced by PHA. The results indicated that4-HMsuppressed, in activated PBMC, the production and mRNA expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor-α, and interferon-γin a concentration-dependent manner. This inhibition was not related to cell viability. While4-HMdid not affect ERK phosphorylation and its downstreamc-fosgene expression in PBMC induced by PHA, it decreased both NF-AT and NF-κB activation. The upstream signaling of NF-AT and NF-κB, intracellular calcium concentrations ([Ca2+]i), and protein kinase C theta (PKCθ) activation in PHA-treated PBMC were reduced by4-HM. The data demonstrated that the suppressant effects of4-HMon cell proliferation in PBMC activated by PHA appeared to be mediated, at least in part, through inhibition of Ca2+mobilization and PKCθactivation, NF-AT and NF-κB activation, and cytokine transcripts and productions of PBMC. We suggested thatA. blazeicontained a potential immunomodulator4-HM.