Epigallocatechin-3-gallate suppresses TNF-α -induced production of MMP-1 and -3 in rheumatoid arthritis synovial fibroblasts

• Published in: Rheumatology international 2008-11, Vol.29 (1), p.23-29
• Main Authors: Yun, Hee-Jin, Yoo, Wan-Hee, Han, Myung-Kwan, Lee, Young-Rae, Kim, Jong-Suk, Lee, Sang-Il
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Arthritis, Rheumatoid - enzymology; Arthritis, Rheumatoid - pathology; Catechin - analogs & derivatives; Catechin - pharmacology; Cells, Cultured; Dose-Response Relationship, Drug; Drug Antagonism; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - pathology; Gene Expression - drug effects; Gene Expression Regulation, Enzymologic - drug effects; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinase 3 - metabolism; Medicine; Medicine & Public Health; Mitogen-Activated Protein Kinases - metabolism; Original Article; Rheumatology; RNA, Messenger - metabolism; Synovial Membrane; Transcription Factor AP-1 - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-008-0597-5

Rheumatoid arthritis (RA) synovial fibroblasts produce matrix metaloproteinases (MMPs), which destruct cartilage and bone in RA joint. Tumor necrosis factor-α (TNF-α) is one of the most important mediator leading to MMP production in RA synovial fibroblasts. Here we show that epigallocatechin-3-Gallate (EGCG) suppresses TNF-α-induced production of MMP-1 and MMP-3 in RA synovial fibroblasts, which was accompanied by inhibition of mitogen activated protein kinase (MAPK) and activator protein-1 (AP-1) pathways. EGCG treatment resulted in dose-dependent inhibition of TNF-α-induced production of MMP-1 and MMP-3 at the protein and mRNA levels in RA synovial fibroblast. EGCG treatment also inhibited TNF-α-induced phosphorylation of MAPKs, such as ERK1/2, p38, JNK. Electrophoretic mobility shift assay revealed that EGCG inhibits binding of AP-1 proteins to its response elements in synovial fibroblast treated. Thus, EGCG may play a role in regulating inflammation and bone destruction in RA patients.