Skip to main content

Advertisement

SpringerLink
Log in

An Extract of the Medicinal Mushroom Agaricus blazei Murill Differentially Stimulates Production of Pro-inflammatory Cytokines in Human Monocytes and Human Vein Endothelial Cells in vitro

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

An extract of the edible mushroom Agaricus blazei Murill (AbM) has known antitumor and anti-infection properties, probably mainly by stimulating mononuclear phagocytes of the native immune system. The aim of this work was to study the effect of AbM on the production by human monocytes and human umbilical vein endothelial cells (EC) of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα), the anti-inflammatory/T regulatory cytokine IL-10 and the pro-Th1 cytokine IL-12. AbM, in concentrations from 1–15%, induced a considerable and dose-dependent increase in production of IL-8, IL-6, TNFα and IL-1β in monocyte cultures. The biosynthesis reached a plateau at a concentration of 10% of AbM, and was most pronounced for the three former cytokines. AbM did also dose-dependently stimulate EC production of IL-8,IL-6 and TNFα, but at lower levels compared with the monocytes. AbM did neither induce synthesis of cytokines IL-10 nor IL-12 in monocytes or EC. Our results demonstrate the differential effect of AbM stimulation on the magnitude of pro-inflammatory cytokines produced by monocytes and EC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

C:

control

References

  1. Huang, N. L. 1997. Brazilian mushroom (Gee Song Rong). In: Cultivation of eight rare and precious gourmet mushrooms. Chinese Agriculture University Press, Huang Edit, pp. 95–101.

  2. Wasser, S. P., and A. L. Weis. 1999. Therapeutic effects of substances occuring in higher Basidiomycetes mushrooms: a modern perspective. Review. Crit. Rev. Immunol. 19:65–96.

    PubMed  CAS  Google Scholar 

  3. Jong, S. C., and R. Donovick. 1989. Antitumour and antiviral substances from fungi. Adv. Appl. Microbiol. 34:183–262.

    Article  PubMed  CAS  Google Scholar 

  4. Kawagashi, H., R. Inagaki, T. Kanao, T. Mizuno, K. Shimura, H. Itoh, T. Hagiwara, and T. Nakamura. 1989. Fractionation and antitumor activity of the water-insoluble residue of Agaricus blazei fruiting bodies. Carbohydr. Res. 186:267–273.

    Article  Google Scholar 

  5. Itoh, H., H. Ito, H. Amano, and H. Noda. 1994. Inhibitory action of a (1→6)-β-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill (“Himematsutake”) on meth A fibrosarcoma-bearing mice and its antitumor mechanism. Jpn. J. Pharmacol. 66:265–271.

    PubMed  CAS  Google Scholar 

  6. Ebina, T., and Y. Fujimiya. 1998. Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice. Biotherapy. 11:259–265.

    Article  PubMed  CAS  Google Scholar 

  7. Ohno, N., M. Furukawa, N. N. Miura, Y. Adachi, M. Motoi, and Y. Yadomae. 2001. Antitumor beta glucan from the cultured fruit body of Agaricus blazei. Biol. Pharm. Bull. 7:820–828.

    Article  Google Scholar 

  8. Fujimiya, Y., Y. Suzuki, Ko-ichi Oshiman, H. Kobori, K. Moriguchi, H. Nakashima, Y. Matumoto, S. Takahara, T. Ebina, and R. Katakura. 1998. Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis. Cancer Immunol. Immunother. 46:147–159.

    Article  PubMed  CAS  Google Scholar 

  9. Sorimachi, K., K. Akimoto, Y. Ikehara, K. Inafuku, A. Okubo, and S. Yamazaki. 2001. Secretion of TNF-α, IL-8 and nitrite oxide by macrohages activated with Agaricus blazei Murill fractions in vitro. Cell Struct. Funct. 26:103–108.

    Article  PubMed  CAS  Google Scholar 

  10. Kuo, Yuh-Chi, Yu-Ling Huang, Chieh-Chih Chen, YZ-Sheng Lin, Kai-An Chuang, and Wei-Jern Tsai. 2002. Cell cycle progression and cytokine gene expression of human peripheral blood mononuclear cells modulated by Agaricus blazei. J. Lab. Clin. Med. 140:176–187.

    Article  PubMed  Google Scholar 

  11. Riggi, S. J., and N. R. Di Luzio. 1961. Identification of a reticuloendothelial stimulating agent in zymosan. Am. J. Physiol. 200:297–300

    PubMed  CAS  Google Scholar 

  12. Bøgwald, J., I. Gouda, J. Hoffmann, O. Larm, R. Larsson, and R. Seljelid. 1984. Stimulatory effect of immobilized glucans on macrophages in vitro. Scand. J. Immunol. 20:355–360.

    Article  PubMed  Google Scholar 

  13. Reynolds, J. A., M. D. Kastello, D. G. Harrington, et al. 1980. Glucan-induced enhancement of host resistance to selected infectious diseases. Infect. Immun. 30:51–57.

    PubMed  CAS  Google Scholar 

  14. Hetland, G., M. Løvik, and H. G. Wiker. 1998. Protective effect of β-glucan against Mycobacterium bovis, BCG infection in Balb/c mice. Scand. J. Immunol. 47:548–553.

    Article  PubMed  CAS  Google Scholar 

  15. Hetland, G., N. Ohno, I. S. Aaberge, and M. Løvik. 2000. Protective effect of β-glucan against systemic Streptococcus pneumonia infection in mice. FEMS Immunol. Med. Microbiol. 27:111–116.

    PubMed  CAS  Google Scholar 

  16. Bernardshaw, S., E. Johnson, and G. Hetland. 2005. An extract of the mushroom Agaricus blazei Murill administered orally protects against systemic Streptococcus pneumoniae infection in mice. Scand. J. Immunol. 62:393–398.

    Article  PubMed  CAS  Google Scholar 

  17. Langeggen, H., E. Namork, E. Johnson, and G. Hetland. 2003. HUVEC take up opsonized zymosan particles and secrete cytokines IL-6 and IL-8 in vitro. FEMS Immunol. Med. Microbiol. 36:55–61.

    Article  PubMed  CAS  Google Scholar 

  18. Trinchieri, G., and F. Gerosa. 1996. Immunoregulation by interleukin-12. J. Leukoc. Biol. 59:505–511.

    PubMed  CAS  Google Scholar 

  19. Haddad, J. J. 2002. Cytokines and related receptor-mediated signaling pathways. Biohem. Biophys. Res. Commun. 297:700–713.

    Article  CAS  Google Scholar 

  20. Horwitz, D. A., S. G. Zheng, and J. D. Gray. 2003. The role of the combination of IL-2 and TGF-β or IL-10 in the generation and function of CD4+CD25+ and CD8+ regulatory T cell subsets. J. Leukoc. Biol. 74:471–478.

    Article  PubMed  CAS  Google Scholar 

  21. Bøyum, A. 1968. Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand. J. Lab. Invest. 21(Suppl 97): 77–89.

    Google Scholar 

  22. Kaplan, G., and G. Gaudernack. 1982. In vitro differentiation of human monocytes. Difference in monocytic phenotypes induced by cultivation on glass or on collagen. J. Exp. Med. 156:1001–1014.

    Article  Google Scholar 

  23. Jaffe, E. A., R. L. Nachman, C. G. Becker, and C. R. Minick. 1973. Culture of human endothelial cells derived from umbilical veins. Identification by morphological and immunological criteria. J. Clin. Lab. Invest. 52:2745–2756.

    CAS  Google Scholar 

  24. Ellertsen, L. K., G. Hetland, and E. Johnson. 2006. Effect of a medical extract from Agaricus blazei Murill on gene expression in human monocytes. Int. Immunopharmacol. 6:133–143.

    Article  PubMed  CAS  Google Scholar 

  25. Chihara, G. 1992. Immunopharmacology of Lentinan, a polysaccharide isolated from Lentinus edodes: its applications as a host defense potentiator. Int. J. Orient. Med. 17:57–77.

    Google Scholar 

  26. Doita, M., L. T. Rasmussen, R. Seljelid, and P. E. Lipsky. 1991. Effect of a soluble aminated β-1,3-D-polyglucose on human monocytes: stimulation of cytokine and prostaglandin E 2 production but not antigen-presenting function. J. Leukoc. Biol. 49:342–351.

    PubMed  CAS  Google Scholar 

  27. Shimizu, S., H. Kitada, H. Yokota, J. Yamakawa, T. Murayama, K. Sugyama, H. Izumi, and N. Yamaguchi. 2002. Activation of the alternative complement pathway by Agaricus blazei Murill. Phytomed. 9:536–545.

    Article  CAS  Google Scholar 

  28. Brown, G. D., P. R. Taylor, D. M. Reid, J. A. Willment, D. L. Williams, L. Martinez-Pomares, S. Y. C. Wong, and S. Gordon. 2002. Dectin-1 is a major β-glucan receptor on macrophages. J. Exp. Med. 196:407–412.

    Article  PubMed  CAS  Google Scholar 

  29. Langeggen, H., K. E. Berge, E. Johnson, and G. Hetland. 2002. Human umbilical vein endothelial cells express complement receptor 1 (CD35) and complement receptor 4 (CD11c/CD18) in vitro. Inflammation. 26:103–110.

    Article  PubMed  CAS  Google Scholar 

  30. Johnson, E., and G. Hetland. 1991. Human umbilical vein endothelial cells synthesize functional C3, C5, C6, C8 and C9 in vitro. Scand. J. Immunol. 33:667–671.

    Article  PubMed  CAS  Google Scholar 

  31. Johnson, E., and G. Hetland. 1988. Mononuclear phagocytes have the potential to synthesize the complete functional complement system. Scand. J. Immunol. 27:489–493.

    Article  PubMed  CAS  Google Scholar 

  32. Cavaillon, J. M. 1994. Cytokines and macrophages. Biomed. Pharmacother. 48:445–453.

    Article  PubMed  CAS  Google Scholar 

  33. Lienenlüke, B., T. Germann, R. A. Kroczek, and M. Hecker. 2000. CD154 stimulation of interleukin-12 synthesis in human endothelial cells. Eur. J. Immunol. 10:2864-2870.

    Article  Google Scholar 

Download references

Acknowledgments

We thank Jan-Inge Herseth and The Department of Air Pollution and Noise at The Norwegian Institute of Public Health, Oslo, for help and facilities. This work was supported by grants from the Research Council at the Surgical Division, Ulleval University Hospital. The AbM extract (“gold label”) was kindly provided by ACE Co., Ltd, Gifu-ken, Japan. From now on this AbM extract is renamed “AndoSan” by the producer.

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Ulleval University Hospital, Kirkeveien 166, 0407, Oslo, Norway

    Soosaipillai Bernardshaw & Egil Johnson

  2. Department of Immunology and Transfusion Medicine, Ulleval University Hospital, Kirkeveien 166, 0407, Oslo, Norway

    Geir Hetland & Anne Merete Aaland Tryggestad

  3. Department of Environmental Immunology, Norwegian Institute of Public Health, Geitmyrsvn. 75, 0462, Oslo, Norway

    Linda Kathrine Ellertsen

  4. Faculty of Medicine, University of Oslo, Oslo, Norway

    Egil Johnson

Authors
  1. Soosaipillai Bernardshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geir Hetland
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Linda Kathrine Ellertsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anne Merete Aaland Tryggestad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Egil Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Egil Johnson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernardshaw, S., Hetland, G., Ellertsen, L.K. et al. An Extract of the Medicinal Mushroom Agaricus blazei Murill Differentially Stimulates Production of Pro-inflammatory Cytokines in Human Monocytes and Human Vein Endothelial Cells in vitro . Inflammation 29, 147–153 (2005). https://doi.org/10.1007/s10753-006-9010-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-006-9010-2

Key words

Search

Navigation