Advertisement

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-γ (IFN-γ), and cyclin D. AB-BDM-2 suppressed, in activated PBMCs, the production and messenger RNA (mRNA) expression of IL-2, IL-4, IFN-γ, 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-γ, 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. (J Lab Clin Med 2002;140:176-87)

      Abbreviations:

      cDNA (complementary DNA), DEPC (diethyl pyrocarbonate), DMSO (dimethylsulfoxide), DTT (dithiothreitol), EDTA (ethylenediaminetetraacetate), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), IL (interleukin), IFN (interferon), iNOS (inducible NO synthetase), LDH (lactate dehydrogenase), mRNA (messenger RNA), NO (nitric oxide), PBMC (peripheral blood mononuclear cell), PBS (phosphate-buffered saline solution), PCR (polymerase chain reaction), PHA (phytohemagglutinin), RT (reverse transcription), SSC (standard saline citrate)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kuo YC
        • Yang NS
        • Chou CJ
        • Lin LC
        • Tsai WJ.
        Regulation of cell proliferation, gene expression, production of cytokines, and cell cycle progression in primary human T lymphocytes by piperlactam S isolated from Piper kadsura.
        Mol Pharmacol. 2000; 58: 1057-1066
        • Kuo YC
        • Sun CM
        • Ou JC
        • Tsai WJ.
        A tumor cell growth inhibitor from Polygonum hypoleucum Ohwi.
        Life Sci. 1997; 61: 2335-2344
        • Farnsworth NR.
        Ethnopharmacology and future drug development: the North American experience.
        J Ethnopharmocol. 1993; 38: 145-152
        • Houghton PJ.
        The role of plants in traditional medicine and current therapy.
        J Altern Complement Med. 1995; 1: 131-143
        • Higaki M
        • Eguchi F
        • Watanabe Y.
        A stable culturing method and pharmacological effects of the Agaricus blazei.
        Folia Pharmacol Jpn. 1997; 110: 98-103
        • Fujimiya Y
        • Suzuki Y
        • Oshiman K
        • Kobori H
        • Moriguchi K
        • Nakashima H
        • et al.
        Selective tumorcidal effect of soluble proteoglucan extracted from the basidomycete Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis.
        Cancer Immunol Immun. 1998; 46: 147-159
        • Fujimiya Y
        • Suzuki Y
        • Katakura R
        • Ebina T.
        Tumor-specific cytocidal and immunopotentiating effects of relatively low molecular weight products derived from the basidomycete Agaricus blazei Murill.
        Anticancer Res. 1999; 19: 113-118
        • Yoshiko O
        • Tetsuta K
        • Kazuko Y
        • Junya O
        • Toshio M.
        Antimutagenic and bactericidal substances in the fruit body of a basidomycete Agaricus blazei, Jun-17.
        Yakugaku Zasshi. 1994; 114: 342-350
        • Kawagishi H
        • Katsumi R
        • Sazawa T
        • Mizuno T
        • Hagiwara T
        • Nakamura T.
        Cytotoxic steroids from the mushroom Agaricus blazei.
        Phytochemistry. 1988; 27: 2777-2779
      1. Immunobiology: The immune system in health and disease. Blackwell Scientific Publications, Oxford, England1994: 49
        • Ajchenbaum F
        • Ando K
        • DeCaprio JA
        • Griffin JD.
        Independent regulation of human D-type cyclin gene expression during G1 phase in primary human T lymphocytes.
        J Biol Chem. 1993; 268: 4113-4119
        • Robb RJ.
        Interleukin-2: the molecule and its function.
        Immunol Today. 1984; 5: 203-209
        • Young HA.
        Regulation of interferon-gamma gene expression.
        J Interf Cytok Res. 1996; 16: 563-568
        • Robb RJ
        • Greene WC.
        Direct demonstration of the identity of T cell growth factor binding protein and TAC antigen.
        J Exp Med. 1983; 158: 1332-1337
        • Fehsel K
        • Kronke KD
        • Meyer KL
        • Huber H
        • Wahn V
        • Kolb-Bachhofen V.
        Nitric oxide induces apoptosis in mouse thymocytes.
        J Immunol. 1995; 155: 2858-2865
        • Arai K
        • Lee F
        • Miyajima A.
        Cytokines: coordinators of immune and inflammatory response.
        Ann Rev Biochem. 1990; 59: 783-836
        • Yang NS
        • Chou CJ
        • Lin LC
        • Tsai WJ
        • Kuo YC.
        Evaluation of Chinese herbs that affect the cell-mediated immunity (III).
        J Chin Med. 1999; 10: 179-188
        • Tsai TF
        • Hsieh CH
        • Lin YS
        • Tsai WJ
        • Kuo YC.
        Enhancement of cell proliferation and cytokines production in human peripheral blood mononuclear cells by extracts from blood-enriching dang-gui decoction.
        J Chin Med. 2001; 12: 191-202
        • Green LC
        • Wanger DA
        • Glogowski J
        • Skipper PL
        • Wishnok JS
        • Tannenbaum SR.
        Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.
        Anal Biochem. 1982; 126: 131-138
        • Kuo YC
        • Sun CM
        • Tsai WJ
        • Ou JC
        • Chen WP
        • Lin CY.
        Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies.
        J Lab Clin Med. 1998; 132: 76-85
        • Saiki PK
        • Scharf S
        • Faloona F
        • Mullis KB
        • Horn G
        • Erlich HA
        • et al.
        Enzymatic amplification of globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.
        Science. 1985; 230: 1350-1354
        • Taniguchi T
        • Matsui H
        • Fujita T
        • Takaoka C
        • Kashima N
        • Yoshimoto R
        • et al.
        Structure and expression of a cloned cDNA for interleukin-2.
        Nature. 1983; 302: 305-310
        • Yokota T
        • Otsuka T
        • Mosmann T
        • Banchereau J
        • Defrance T
        • Blanchard D
        • et al.
        Isolation and characterization of a human interleukin cDNA clone homologous to mouse B-cell stimulatory factor 1 that expresses B-cell and T-cell stimulatory activities.
        Proc Natl Acad Sci U S A. 1986; 83: 5894-5898
        • Gray PW
        • Aggarwal BB
        • Benton CV
        • Bringman TS
        • Henzel WJ
        • Jarrett JA
        • et al.
        Expression of human immune interferon cDNA in E. coli and monkey cells.
        Nature. 1982; 295: 503-508
        • Park CS
        • Park R
        • Krishna G.
        Constitutive expression and structural diversity of inducible isoform of nitirc oxide synthetase in human tissues.
        Life Sci. 1996; 59: 219-225
      2. Kuby Immunology. Freeman, New York2000: 395-412
        • Muro Y.
        Autoantibodies in atopic dermatitis.
        J Dermatol Sci. 2001; 25: 171-178
        • Park CS
        • Park R
        • Krishna G.
        Constitutive expression and structural diversity of inducible isoform of nitric oxide synthetase in human tissues.
        Life Sci. 1996; 59: 219-225
        • Schreiber SL
        • Crabtree GR.
        The mechanism of action of cyclsporin A and FK 506.
        Immunol Today. 1992; 13: 136-142
        • Yang LY
        • Chen A
        • Kuo YC
        • Lin CY.
        Efficacy of a pure compound H1A extracted from Cordyceps sinensis on autoimmune disease of MRL lpr/lpr mice.
        J Lab Clin Med. 1999; 134: 492-500