title: Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1 beta-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes.
abstract: We have previously shown that green tea polyphenols inhibit the onset and severity of collagen II-induced arthritis in mice. In the present study, we report the pharmacological effects of green tea polyphenol epigallocatechin-3-gallate (EGCG), on interleukin-1 beta (IL-1 beta)-induced expression and activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in human chondrocytes derived from osteoarthritis (OA) cartilage. Stimulation of human chondrocytes with IL-1 beta (5 ng/ml) for 24 h resulted in significantly enhanced production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) when compared to untreated controls (p <.001). Pretreament of human chondrocytes with EGCG showed a dose-dependent inhibition in the production of NO and PGE(2) by 48% and 24%, respectively, and correlated with the inhibition of iNOS and COX-2 activities (p <.005). In addition, IL-1 beta-induced expression of iNOS and COX-2 was also markedly inhibited in human chondrocytes pretreated with EGCG (p <.001). Parallel to these findings, EGCG also inhibited the IL-1 beta-induced LDH release in chondrocytes cultures. Overall, the study suggests that EGCG affords protection against IL-1 beta-induced production of catabolic mediators NO and PGE(2) in human chondrocytes by regulating the expression and catalytic activity of their respective enzymes. Furthermore, our results also indicate that ECGC may be of potential therapeutic value for inhibiting cartilage resorption in arthritic joints.
authors.affiliation: Department of Orthopedics, Case Western Reserve University, Cleveland, OH 44106-4946, USA.
authors.forename: Salahuddin
authors.initials: S
authors.lastname: Ahmed
authors.forename: Ayesha
authors.initials: A
authors.lastname: Rahman
authors.forename: Absarul
authors.initials: A
authors.lastname: Hasnain
authors.forename: Matthew
authors.initials: M
authors.lastname: Lalonde
authors.forename: Victor M
authors.initials: VM
authors.lastname: Goldberg
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Haqqi
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology; D051546:Cyclooxygenase 2; D003864:Depression, Chemical; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010003:Osteoarthritis / Q000378:metabolism / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013662:Tea / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D013662:Tea; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; D007770:L-Lactate Dehydrogenase; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone