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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 2004; 308(2):767-73JP

Abstract

Interleukin-1beta (IL-1beta)-induced inflammatory response in arthritic joints include the enhanced expression and activity of matrix metalloproteinases (MMPs), and their matrix degrading activity contribute to the irreversible loss of cartilage and may also be associated with sustained chronic inflammation. We have earlier shown that green tea (Camellia sinensis) polyphenol epigallocatechin-3-gallate (EGCG) was non-toxic to human chondrocytes [Singh R, Ahmed S, Islam N, Goldberg VM, and Haqqi TM (2002) Arthritis Rheum 46: 2079-2086] and inhibits the expression of inflammatory mediators in arthritic joints [Haqqi TM, Anthony DD, Gupta S, Ahmed N, Lee MS, Kumar GK, and Mukhtar H (1999) Proc Natl Acad Sci USA 96: 4524-4529]. Here we show that EGCG at micromolar concentrations was highly effective in inhibiting the IL-1beta-induced glycosaminoglycan (GAG) release from human cartilage explants in vitro. EGCG also inhibited the IL-1beta-induced mRNA and protein expression of MMP-1 and MMP-13 in human chondrocytes. Importantly, EGCG showed a differential, dose-dependent inhibitory effect on the expression and activity of MMP-13 and MMP-1. A similar differential dose-dependent inhibition of transcription factors NF-kappaB and AP-1 by EGCG was also noted. These results for the first time demonstrate a differential dose-dependent effect of EGCG on the expression and activity of MMPs and on the activities of transcription factors NF-kappaB and AP-1 and provide insights into the molecular basis of the reported anti-inflammatory effects of EGCG. These results also suggest that EGCG or compounds derived from it may be therapeutically effective inhibitors of IL-1beta-induced production of matrix-degrading enzymes in arthritis.

Authors+Show Affiliations

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4946, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14600251

Citation

Ahmed, Salahuddin, et al. "Green Tea Polyphenol Epigallocatechin-3-gallate (EGCG) Differentially Inhibits Interleukin-1 Beta-induced Expression of Matrix Metalloproteinase-1 and -13 in Human Chondrocytes." The Journal of Pharmacology and Experimental Therapeutics, vol. 308, no. 2, 2004, pp. 767-73.
Ahmed S, Wang N, Lalonde M, et al. 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. 2004;308(2):767-73.
Ahmed, S., Wang, N., Lalonde, M., Goldberg, V. M., & Haqqi, T. M. (2004). Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes. The Journal of Pharmacology and Experimental Therapeutics, 308(2), pp. 767-73.
Ahmed S, et al. 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. 2004;308(2):767-73. PubMed PMID: 14600251.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes. AU - Ahmed,Salahuddin, AU - Wang,Naizhen, AU - Lalonde,Mathew, AU - Goldberg,Victor M, AU - Haqqi,Tariq M, Y1 - 2003/11/04/ PY - 2003/11/6/pubmed PY - 2004/3/12/medline PY - 2003/11/6/entrez SP - 767 EP - 73 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 308 IS - 2 N2 - Interleukin-1beta (IL-1beta)-induced inflammatory response in arthritic joints include the enhanced expression and activity of matrix metalloproteinases (MMPs), and their matrix degrading activity contribute to the irreversible loss of cartilage and may also be associated with sustained chronic inflammation. We have earlier shown that green tea (Camellia sinensis) polyphenol epigallocatechin-3-gallate (EGCG) was non-toxic to human chondrocytes [Singh R, Ahmed S, Islam N, Goldberg VM, and Haqqi TM (2002) Arthritis Rheum 46: 2079-2086] and inhibits the expression of inflammatory mediators in arthritic joints [Haqqi TM, Anthony DD, Gupta S, Ahmed N, Lee MS, Kumar GK, and Mukhtar H (1999) Proc Natl Acad Sci USA 96: 4524-4529]. Here we show that EGCG at micromolar concentrations was highly effective in inhibiting the IL-1beta-induced glycosaminoglycan (GAG) release from human cartilage explants in vitro. EGCG also inhibited the IL-1beta-induced mRNA and protein expression of MMP-1 and MMP-13 in human chondrocytes. Importantly, EGCG showed a differential, dose-dependent inhibitory effect on the expression and activity of MMP-13 and MMP-1. A similar differential dose-dependent inhibition of transcription factors NF-kappaB and AP-1 by EGCG was also noted. These results for the first time demonstrate a differential dose-dependent effect of EGCG on the expression and activity of MMPs and on the activities of transcription factors NF-kappaB and AP-1 and provide insights into the molecular basis of the reported anti-inflammatory effects of EGCG. These results also suggest that EGCG or compounds derived from it may be therapeutically effective inhibitors of IL-1beta-induced production of matrix-degrading enzymes in arthritis. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/14600251/Green_tea_polyphenol_epigallocatechin_3_gallate__EGCG__differentially_inhibits_interleukin_1_beta_induced_expression_of_matrix_metalloproteinase_1_and__13_in_human_chondrocytes_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14600251 DB - PRIME DP - Unbound Medicine ER -