Skip to main content

Advertisement

SpringerLink
Log in

Effects of (−)-epigallocatechin-3-gallate on cyclooxygenase 2, PGE2, and IL-8 expression induced by IL-1β in human synovial fibroblasts

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The objective of this study was to examine the effects of (−)-epigallocatechin-3-gallate (EGCG) on cyclooxygenase 2 (COX-2), prostaglandin E2 (PGE2), and interleukin 8 (IL-8) expression induced by IL-1β in human synovial fibroblasts. Cells were enzymatically isolated from synovial tissue taken from patients undergoing joint replacement surgery for osteoarthritis. Reverse transcriptase-polymerase chain reaction, immunocytochemistry, and western blotting were used to assess the COX-2 gene and protein expression with the associated mechanisms. PGE2 and IL-8 secretion into the culture medium was assayed by enzyme-linked immunosorbent assay. COX-2 upregulation in synovial fibroblasts induced by IL-1β was significantly suppressed by EGCG in a dose-dependent manner. PGE2 and IL-8 secretion was also induced by IL-1β stimulation and significantly suppressed by EGCG. The mechanism was associated with the phosphorylation of IKKβ. EGCG may inhibit the expression of inflammatory mediators, such as COX-2, PGE2, and IL-8, induced by IL-1β in human synovial fibroblasts. EGCG may be of value in the treatment of synovial inflammation.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ahmed S, Pakozdi A, Koch AE (2006) Regulation of interleukin-1β-induced chemokine production and matrix metalloproteinase 2 activation by epigallocatechin-3-gallate in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 54:2393–2401

    Article  CAS  PubMed  Google Scholar 

  2. Muñoz-Fernández S, Martín J, Martín-Mola E, García-Rodriguez MC, Cantalejo M, Fontán G, Ferreira A (2001) Soluble HLA class I antigens in serum and synovial fluid from patients with rheumatoid arthritis and other arthropathies. Rheumatology 40:1365–1369

    Article  PubMed  Google Scholar 

  3. Bröker BM, Edwards JC, Fanger MW, Lydyard PM (1999) The prevalence and distribution of macrophages bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in synovium. Scand J Rheumatol 19:123–135

    Article  Google Scholar 

  4. Eastgate JA, Symons JA, Wood NC, Grinlinton FM, di Giovine FS, Duff GW (1988) Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet 2:706–709

    Article  CAS  PubMed  Google Scholar 

  5. van Lent PL, Holthuysen AE, van den Bersselaar L, van Rooijen N, van de Putte LB, van den Berg WB (1995) Role of macrophage-like synovial lining cells in localization and expression of experimental arthritis. Scand J Rheumatol Suppl 101:83–89

    Article  PubMed  Google Scholar 

  6. Kalliolias GD, Liossis SN (2008) The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to adult-onset Still’s disease and systemic-onset juvenile idiopathic arthritis. Expert Opin Invest Drugs 17:349–359

    Article  CAS  Google Scholar 

  7. Van der Kraan PM, van den Berg WB (2000) Anabolic and destructive mediators in osteoarthritis. Cur Opin Clin Nutr Metab Care 3:205–211

    Article  Google Scholar 

  8. Lee HS, Lee CH, Tsai HC, Salter DM (2009) Inhibition of cyclooxygenase 2 expression by diallyl sulfide on joint inflammation induced by urate crystal and IL-1beta. Osteoarthr Cartil. doi:10.1016/j.joca.2008.05.010

  9. Chen D, Milacic V, Chen MS, Wan SB, Lam WH, Huo C, Landis-Piwowar KR, Cui QC, Wali A, Chan TH, Dou QP (2008) Tea polyphenols, their biological effects and potential molecular targets. Histol Histopathol 23:487–496

    PubMed  Google Scholar 

  10. Chen YF, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, Taylor RS (2008) Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess 2:1–278

    Google Scholar 

  11. Katiyar SK, Challa A, McCormick TS, Cooper KD, Mukhtar H (1999) Prevention of UVB-induced immunosuppression in mice by the green tea polyphenol (−)-epigallocatechin-3-gallate may be associated with alterations in IL-10 and IL-12 production. Carcinogenesis 20:2117–2124

    Article  CAS  PubMed  Google Scholar 

  12. Katiyar SK, Matsui MS, Elmets CA, Mukhtar H (1999) Polyphenolic antioxidant (−)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Photochem Photobiol 69:148–153

    CAS  PubMed  Google Scholar 

  13. Katiyar SK, Afaq F, Perez A, Mukhtar H (2001) Green tea polyphenol (−)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress. Carcinogenesis 22:287–294

    Article  CAS  PubMed  Google Scholar 

  14. Katiyar SK, Mukhtar H (2001) Green tea polyphenol (−)-epigallocatechin-3-gallate treatment to mouse skin prevents UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress. J Leukoc Biol 69:719–726

    CAS  PubMed  Google Scholar 

  15. Devika PT, Stanely Mainzen Prince P (2008) Protective effect of (−)-epigallocatechin-gallate (EGCG) on lipid peroxide metabolism in isoproterenol induced myocardial infarction in male Wistar rats: a histopathological study. Biomed Pharmacother 62:701–708

    Article  CAS  PubMed  Google Scholar 

  16. Ramadass P, Meerarani P, Toborek M, Robertson LW, Hennig B (2003) Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells. Toxicol Sci 76:212–219

    Article  CAS  PubMed  Google Scholar 

  17. Yang F, Oz HS, Barve S, de Villiers WJ, McClain CJ, Varilek GW (2001) The green tea polyphenol (−)-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol 60:528–533

    CAS  PubMed  Google Scholar 

  18. Kim J, Hwang JS, Cho YK, Han Y, Jeon YJ, Yang KH (2001) Protective effects of (−)-epigallocatechin-3-gallate on UVA- and UVB-induced skin damage. Skin Pharmacol Appl Skin Physiol 14:11–19

    CAS  PubMed  Google Scholar 

  19. Albrecht DS, Clubbs EA, Ferruzzi M, Bomser JA (2008) Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation. Chem Biol Interact 171:89–95

    Article  CAS  PubMed  Google Scholar 

  20. Tang Y, Zhao DY, Elliott S, Zhao W, Curiel TJ, Beckman BS, Burow ME (2007) Epigallocatechin-3 gallate induces growth inhibition and apoptosis in human breast cancer cells through survivin suppression. Int J Oncol 31:705–711

    CAS  PubMed  Google Scholar 

  21. Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS (2003) Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63:7563–7570

    CAS  PubMed  Google Scholar 

  22. Nam S, Smith DM, Dou QP (2001) Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo. J Biol Chem 276:13322–13330

    Article  CAS  PubMed  Google Scholar 

  23. Shimizu M, Deguchi A, Joe AK, Mckoy JF, Moriwaki H, Weinstein IB (2005) EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. J Exp Ther Oncol 5:69–78

    PubMed  Google Scholar 

  24. Hussain T, Gupta S, Adhami VM, Mukhtar H (2005) Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells. Int J Cancer 113:660–669

    Article  CAS  PubMed  Google Scholar 

  25. Widlansky ME, Hamburg NM, Anter E, Holbrook M, Kahn DF, Elliott JG, Keaney JF Jr, Vita JA (2007) Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J Am Coll Nutr 26:95–102

    CAS  PubMed  Google Scholar 

  26. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL (2004) Nutrition Committee of the American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Antioxidant vitamin supplements and cardiovascular disease. Circulation 110:637–641

    Article  CAS  PubMed  Google Scholar 

  27. Lindblad S, Hedfors E (1987) Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum 30:1081–1088

    Article  CAS  PubMed  Google Scholar 

  28. Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M (2005) Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis—results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage 13:361–367

    Article  CAS  PubMed  Google Scholar 

  29. Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M (1997) Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol 24:365–371

    CAS  PubMed  Google Scholar 

  30. Pelletier JP, Martel-Pelletier J, Abramson SB (2001) Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 44:1237–1247

    Article  CAS  PubMed  Google Scholar 

  31. Martel-Pelletier J, Pelletier JP, Fahmi H (2003) Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum 33(3):155–167

    Article  CAS  PubMed  Google Scholar 

  32. Kaneko S, Satoh T, Chiba J, Ju C, Inoue K, Kagawa J (2000) Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther 6:71–79

    Article  CAS  PubMed  Google Scholar 

  33. Ahmed S, Wang N, Lalonde M, Goldberg VM, Haqqi TM (2004) Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes. J Pharmacol Exp Ther 308:767–773

    Article  CAS  PubMed  Google Scholar 

  34. Adcocks C, Collin P, Buttle DJ (2002) Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro. J Nutr 132:341–346

    CAS  PubMed  Google Scholar 

  35. Agro A, Langdon C, Smith F, Richards CD (1996) Prostaglandin E2 enhances interleukin 8 (IL-8) and IL-6 but inhibits GMCSF production by IL-1 stimulated human synovial fibroblasts in vitro. J Rheumatol 23:862–868

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Science Council (NSC97-2320-B-016-009-MY3), National Defense Medical Center (DOD96-13-01), and Tri-Service General Hospital, Taiwan (TSGH-C96-1-S04).

Author information

Authors and Affiliations

  1. Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan

    Guo-Shu Huang

  2. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City 104, Taiwan

    Ching-Ya Tseng

  3. Department of Orthopaedic Surgery, Taipei Medical University Hospital, Taipei City 110, Taiwan

    Chian-Her Lee

  4. School of Public Health, National Defense Medical Center, Taipei City 114, Taiwan

    Sui-Long Su

  5. Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd, Neihu District, Taipei City 114, Taiwan

    Herng-Sheng Lee

Authors
  1. Guo-Shu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ching-Ya Tseng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chian-Her Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sui-Long Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Herng-Sheng Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Herng-Sheng Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, GS., Tseng, CY., Lee, CH. et al. Effects of (−)-epigallocatechin-3-gallate on cyclooxygenase 2, PGE2, and IL-8 expression induced by IL-1β in human synovial fibroblasts. Rheumatol Int 30, 1197–1203 (2010). https://doi.org/10.1007/s00296-009-1128-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-009-1128-8

Keywords

Search

Navigation