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

Abstract

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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Kim SS, Kim YS (1990) Korean mushrooms. Yupoong Pub, Seoul, pp 298–299

    Google 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

    CAS  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

    Article  CAS  Google Scholar 

  4. 4.

    Lin ZB (2005) Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci Review 99:144–153

    Article  CAS  Google 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

    PubMed  Article  CAS  Google 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

    PubMed  Article  CAS  Google 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

    PubMed  CAS  Google 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

    PubMed  CAS  Google 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

    Article  Google 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

    PubMed  Article  CAS  Google 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

    PubMed  CAS  Article  Google 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

    PubMed  Article  CAS  Google 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

    PubMed  CAS  Google 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

    PubMed  Article  CAS  Google 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

    Article  Google 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

    PubMed  CAS  Article  Google 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

    PubMed  CAS  Article  Google 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

    PubMed  CAS  Google 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

    PubMed  Article  CAS  Google 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

    PubMed  CAS  Google 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

    PubMed  Article  CAS  Google 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 190:67–92

    PubMed  CAS  Google 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 Review

    Google Scholar 

  24. 24.

    Koch AE, Kunkel SL, Strieter RM (1995) Cytokines in rheumatoid arthritis. J Investig Med Review 43:28–38

    CAS  Google 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

    PubMed  Article  CAS  Google 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

    PubMed  CAS  Google 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

    PubMed  CAS  Google 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

    PubMed  CAS  Google 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 6:162–170

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgment

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

Author information

Affiliations

Authors

Corresponding author

Correspondence to C. S. Lau.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ho, Y.W., Yeung, J.S.L., Chiu, P.K.Y. et al. Ganoderma lucidum polysaccharide peptide reduced the production of proinflammatory cytokines in activated rheumatoid synovial fibroblast. Mol Cell Biochem 301, 173–179 (2007). https://doi.org/10.1007/s11010-006-9409-y

Download citation

Keywords

  • Ganoderma lucidum
  • Rheumatoid arthritis
  • Synovial fibroblast
  • Cytokines
  • NF-κB
  • Inflammation