Molecular and Cellular Biochemistry

, Volume 301, Issue 1–2, pp 173–179 | Cite as

Ganoderma lucidum polysaccharide peptide reduced the production of proinflammatory cytokines in activated rheumatoid synovial fibroblast

  • Y. W. Ho
  • J. S. L. Yeung
  • P. K. Y. Chiu
  • W. M. Tang
  • Z. B. Lin
  • R. Y. K. Man
  • C. S. LauEmail author


The aim of the current study was to elucidate the potential therapeutic effect of Ganoderma lucidum polysaccharide peptide (GL-PP) in rheumatoid arthritis (RA). The effects of GL-PP on cell proliferation and cytokine production were studied in RA synovial fibroblasts (RASF). GL-PP significantly inhibited the proliferation of RASF. Following the incubation with GL-PP, production of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 in RASF were significantly increased as expressed as percentage change from basal values. However, the actual effects were minimal due to the low basal values. When RASF were activated by IL-1β or lipopolysaccharides, IL-8 and MCP-1 production increased many folds. GL-PP significantly suppressed their productions. The inhibitory effects of GL-PP on cytokine production in RASF were at least in part, by inhibiting the nuclear factor-kappa B (NF-κB) transcription pathway. Our results demonstrated that GL-PP had the unique ability to modulate cytokine production in RASF and warrants further investigation into its mechanism of action.


Ganoderma lucidum Rheumatoid arthritis Synovial fibroblast Cytokines NF-κB Inflammation 



This study was supported by University Grants Council of Hong Kong.


  1. 1.
    Kim SS, Kim YS (1990) Korean mushrooms. Yupoong Pub, Seoul, pp 298–299Google Scholar
  2. 2.
    Wasser SP, Weis AL (1999) Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol Review 19:65–96 Google Scholar
  3. 3.
    Lakshmi B, Ajith TA, Sheena N, Gunapalan N, Janardhanan KK (2003) Antiperoxidative, anti-inflammatory, and antimutagenic activities of ethanol extract of the mycelium of Ganoderma lucidum occurring in South India. Terato Carcinog Mutagen Suppl 1 1:85–97 CrossRefGoogle Scholar
  4. 4.
    Lin ZB (2005) Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci Review 99:144–153 CrossRefGoogle Scholar
  5. 5.
    Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS (1997) The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer 70:699–705 PubMedCrossRefGoogle Scholar
  6. 6.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324 PubMedCrossRefGoogle Scholar
  7. 7.
    Harigai M, Kitani A, Hara M, Hirose T, Norioka K, Suzuki K et al (1988) Rheumatoid adherent synovial cells produce B cell differentiation factor activity neutralizable by antibody to B cell stimulatory factor-2 interleukin 6. J Rheumatol 15:1616–1622 PubMedGoogle Scholar
  8. 8.
    You YH, Lin ZB (2002) Protective effects of Ganoderma lucidum polysaccharides peptide on injury of macrophages induced by reactive oxygen species. Acta Pharmacol Sin 23:787–791 PubMedGoogle Scholar
  9. 9.
    Gruendker C, Schulz K, Guenthert Andreas R, Emons G (2000) Luteinizing hormone-releasing hormone induces nuclear factor kappaB-activation and inhibits apoptosis in ovarian cancer cells. J Clin Endocrinol Metab 85:3815–3820 CrossRefGoogle Scholar
  10. 10.
    Shibuta K, Begum NA, Mori M, Shimoda K, Akiyoshi T, Barnard GF (1997) Reduced expression of the CXC chemokine hIRH/SDF-1alpha mRNA in hepatoma and digestive tract cancer. Int J Cancer 73:656–662 PubMedCrossRefGoogle Scholar
  11. 11.
    Guerne PA, Zuraw BL, Vaughan JH, Carson DA, Lotz M (1989) Synovium as a source of interleukin 6 in vitro. Contribution to local and systemic manifestations of arthritis. J Clin Invest 83:585–592 PubMedCrossRefGoogle Scholar
  12. 12.
    Volin MV, Campbell PL, Connors MA, Woodruff DC, Koch AE (2002) The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production. Exp Mol Pathol 73:84–92 PubMedCrossRefGoogle Scholar
  13. 13.
    Rao JK, Mihaliak K, Kroenke K, Bradley J, Tierney WM, Weinberger M (1999) Use of complementary therapies for arthritis among patients of rheumatologists. Ann Intern Med 131:409–416 PubMedGoogle Scholar
  14. 14.
    Lai NS, Lin RH, Lai RS, Kun UC, Leu SC (2001) Prevention of autoantibody formation and prolonged survival in New Zealand Black/New Zealand White F1 mice with an ancient Chinese herb, Ganoderma tsugae. Lupus 10:461–465 PubMedCrossRefGoogle Scholar
  15. 15.
    Tasaka K, Mio M, Izushi K, Akagi M, Makino T (1998) Anti-allergic constituents in the culture medium of Ganoderma lucidum. (II). The inhibitory effect of cyclooctasulfur on histamine release. Agents Actions 23:157–160 CrossRefGoogle Scholar
  16. 16.
    Kino K, Sone T, Watanabe J, Yamashita A, Tsuboi H, Miyajima H (1991) Immunomodulator, LZ-8, prevents antibody production in mice. Int J Immunopharmacol 13:1109–1115 PubMedCrossRefGoogle Scholar
  17. 17.
    Tao J, Feng KY (1990) Experimental and clinical studies on inhibitory effect of ganoderma lucidum on platelet aggregation. J Tongji Med Univ 10:240–243 PubMedCrossRefGoogle Scholar
  18. 18.
    Kim RS, Kim HW, Kim BK (1997) Suppressive effects of Ganoderma lucidum on proliferation of peripheral blood mononuclear cells. Mol Cells 7:52–57 PubMedGoogle Scholar
  19. 19.
    Mauri C, Gray D, Mushtaq N, Londei M (2003) Prevention of arthritis by interleukin 10-producing B cells. J Exp Med 197:489–501 PubMedCrossRefGoogle Scholar
  20. 20.
    Yssel H, De Waal Malefyt R, Roncarolo MG, Abrams JS, Lahesmaa R, Spits H et al (1992) IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol 149:2378–2384 PubMedGoogle Scholar
  21. 21.
    Chomarat P, Banchereau J, Miossec P (1995) Differential effects of interleukins 10 and 4 on the production of interleukin-6 by blood and synovium monocytes in rheumatoid arthritis. Arthritis Rheum 38:1046–1054 PubMedCrossRefGoogle Scholar
  22. 22.
    Schwachula A, Riemann D, Kehlen A, Langner J (1994) Characterization of the immunophenotype and functional properties of fibroblast-like synoviocytes in comparison to skin fibroblasts and umbilical vein endothelial cells. Immunobiology 190:67–92PubMedGoogle Scholar
  23. 23.
    Brennan FM, Field M, Chu CQ, Feldmann M, Maini RN (1991) Cytokine expression in rheumatoid arthritis. Br J Rheumatol 30 Suppl 1:76–80 ReviewGoogle Scholar
  24. 24.
    Koch AE, Kunkel SL, Strieter RM (1995) Cytokines in rheumatoid arthritis. J Investig Med Review 43:28–38Google Scholar
  25. 25.
    Gilman SC, Chang J, Zeigler PR, Uhl J, Mochan E (1988) Interleukin-1 activates phospholipase A2 in human synovial cells. Arthritis Rheum 31:126–130 PubMedCrossRefGoogle Scholar
  26. 26.
    Schumacher RH (1993) Primer on the rheumatic diseases, 10th edn. Arthritis Foundation, Atlanta, GA, pp 1–50 Google Scholar
  27. 27.
    Roshak A, Mochan E, Marshall LA (1996) Suppression of human synovial fibroblast 85 kDa phospholipase A2 by antisense reduces interleukin-1 beta induced prostaglandin E2. J Rheumatol 23:420–427 PubMedGoogle Scholar
  28. 28.
    Gao XX, Wang BX, Fei XF, Zhang J, Gong YJ, Minami M et al (2000) Effects of polysaccharides (F10-c) from mycelium of Ganoderma tsugae on proinflammatory cytokine production by THP-1 cells and human PBMC(II). Acta Pharmacol Sin 21:1186–1192 PubMedGoogle Scholar
  29. 29.
    Georganas C, Liu H, Perlman H, Hoffmann A, Thimmapaya B, Pope RM (2000) Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the dominant role for NF-kappa B but not C/EBP beta or c-Jun. J immunol 165:7199–7206 PubMedGoogle Scholar
  30. 30.
    Loetscher P, Dewald B, Baggiolini M, Seitz M (1994) Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes. Effects of anti-rheumatic drugs. Cytokine 6:162–170PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Y. W. Ho
    • 1
  • J. S. L. Yeung
    • 2
  • P. K. Y. Chiu
    • 3
  • W. M. Tang
    • 3
  • Z. B. Lin
    • 4
  • R. Y. K. Man
    • 1
  • C. S. Lau
    • 2
    Email author
  1. 1.Department of PharmacologyUniversity of Hong KongHong Kong SARHong Kong
  2. 2.Department of MedicineUniversity of Hong KongHong Kong SARHong Kong
  3. 3.Department of Orthopaedics and TraumatologyUniversity of Hong KongHong Kong SARHong Kong
  4. 4.Department of Pharmacology, Peking University Health Science CenterSchool of Basic Medical SciencesBeijingChina

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