title: Cell cycle progression and cytokine gene expression of human peripheral blood mononuclear cells modulated by Agaricus blazei.
abstract: We selected Agaricus blazei Murill, used in the treatment of tissue inflammation and cancer in traditional Chinese medicine, to test its immunopharmacological activity. The effects of A. blazei extracted fractions (AB-BDM-1 to AB-BDM-10) on human peripheral blood mononuclear cell (PBMC) proliferation were determined on the basis of the uptake of tritiated thymidine. The results indicated that AB-BDM-2 fraction suppressed PBMC proliferation activated with phytohemagglutinin. The inhibitory action of AB-BDM-2 did not involve direct cytotoxicity. Cell-cycle analysis indicated that AB-BDM-2 arrested the cell-cycle progression of activated PBMCs from the G1 transition to the S phase. In an attempt to further localize the point in the cell cycle where arrest occurred, we examined a set of key regulatory events leading to the G1/S boundary, including gene expression of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and cyclin D. AB-BDM-2 suppressed, in activated PBMCs, the production and messenger RNA (mRNA) expression of IL-2, IL-4, IFN-gamma, and cyclin D in dose-dependent fashion. AB-BDM-2 did not affect nitric oxide production or levels of inducible nitric oxide synthetase mRNA in PBMCs stimulated with PHA. The suppressant effects of AB-BDM-2 on the proliferation of PBMC activated by PHA therefore appear to be mediated, at least in part, through inhibition of early transcripts of PBMCs, especially those of important cytokines IL-2, IL-4, and IFN-gamma, cyclin D, and the arrest of cell-cycle progression in the cells. We suggest that immunomodulatory agents are contained in AB-BDM-2 separated from A. blazei.
authors.affiliation: National Research Institute of Chinese Medicine, the Institute of Biology, and the Department of Nutrition and Food Sciences, Fu-Jen University, Taipei, Taiwan. kuo9111@cma23.nricm.edu.tw
authors.forename: Yuh-Chi
authors.initials: YC
authors.lastname: Kuo
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Huang
authors.forename: Chieh-Chih
authors.initials: CC
authors.lastname: Chen
authors.forename: Yz-Sheng
authors.initials: YS
authors.lastname: Lin
authors.forename: Kai-An
authors.initials: KA
authors.lastname: Chuang
authors.forename: Wei-Jern
authors.initials: WJ
authors.lastname: Tsai
mesh_terms: D000328:Adult; D000364:Agaricus / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005591:Chemical Fractionation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008516:Medicine, Chinese Traditional; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
chemical_list: D016207:Cytokines; D010936:Plant Extracts; D012333:RNA, Messenger; D009569:Nitric Oxide