Cell cycle progression and cytokine gene expression of human peripheral blood mononuclear cells modulated by Agaricus blazei.
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.
Kuo
Yuh-Chi
YC
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
Huang
Yu-Ling
YL
Chen
Chieh-Chih
CC
Lin
Yz-Sheng
YS
Chuang
Kai-An
KA
Tsai
Wei-Jern
WJ
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
D016207:Cytokines; D010936:Plant Extracts; D012333:RNA, Messenger; D009569:Nitric Oxide