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Epigallocatechin‐3‐gallate selectively inhibits interleukin‐1 β‐induced activation of mitogen activated protein kinase subgroup c‐ Jun N ‐terminal kinase in human osteoarthritis chondrocytes
Author(s) -
Singh Rashmi,
Ahmed Salahuddin,
Malemud Charles J.,
Goldberg Victor M.,
Haqqi Tariq M.
Publication year - 2003
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/s0736-0266(02)00089-x
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , kinase , protein kinase a , microbiology and biotechnology , chemistry , mitogen activated protein kinase , phosphorylation , mitogen activated protein kinase kinase , biology
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‐inflammtory effects, in modulating the IL‐1β‐induced activation of MAPK's in human chondrocytes. We discovered that EGCG inhibited the IL‐1β‐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‐1β, 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‐1β 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‐1β‐induced catabolic effects in OA chondrocytes that are dependent on JNK activity. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.