Epigallocatechin-3-gallate selectively inhibits interleukin-1beta-induced activation of mitogen activated protein kinase subgroup c-Jun N-terminal kinase in human osteoarthritis chondrocytes.
Activation of mitogen activated protein kinases (MAPK) is a critical event in pro-inflammatory cytokine-induced signaling cascade in synoviocytes and chondrocytes that lead to the production of several mediators of cartilage damage in an arthritic joint. Green tea (Camellia sinensis) is a widely consumed beverage and we earlier showed that polyphenols present in green tea (GTP) inhibit the development of inflammation and cartilage damage in an animal model of arthritis. In this study we evaluated the role of epigallocatechin-3-gallate (EGCG), a green tea polyphenol which mimics its anti-inflammatory effects, in modulating the IL-1beta-induced activation of MAPK's in human chondrocytes. We discovered that EGCG inhibited the IL-1beta-induced phosphorylation of c-Jun N-terminal kinase (JNK) isoforms, accumulation of phospho-c-Jun and DNA binding activity of AP-1 in osteoarthritis (OA) chondrocytes. Also IL-1beta, but not EGCG, induced the expression of JNK p46 without modulating the expression of JNK p54 in OA chondrocytes. In immunecomplex kinase assays, EGCG completely blocked the substrate phosphorylating activity of JNK but not of p38-MAPK. EGCG had no inhibitory effect on the activation of extracellular signal-regulated kinase p44/p42 (ERKp44/p42) or p38-MAPK in OA chondrocytes. EGCG or IL-1beta did not alter the total non-phosphorylated levels of either p38-MAPK or ERKp44/p42 in OA chondrocytes. These are novel findings and indicate that EGCG may be of potential benefit in inhibiting IL-1beta-induced catabolic effects in OA chondrocytes that are dependent on JNK activity.
Singh
Rashmi
R
Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106-4946, USA.
Ahmed
Salahuddin
S
Malemud
Charles J
CJ
Goldberg
Victor M
VM
Haqqi
Tariq M
TM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000970:Antineoplastic Agents; D007375:Interleukin-1; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D002392:Catechin; D004247:DNA; C045651:epigallocatechin gallate; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases