Ahmed Salahuddin, Rahman Ayesha, Hasnain Absarul, Lalonde Matthew, Goldberg Victor M, Haqqi Tariq M
Department of Orthopedics, Case Western Reserve University, Cleveland, OH 44106-4946, USA.
Free Radic Biol Med. 2002 Oct 15;33(8):1097-105. doi: 10.1016/s0891-5849(02)01004-3.
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.
我们之前已经表明，绿茶多酚可抑制小鼠中Ⅱ型胶原诱导的关节炎的发病和严重程度。在本研究中，我们报告了绿茶多酚表没食子儿茶素-3-没食子酸酯（EGCG）对源自骨关节炎（OA）软骨的人软骨细胞中白细胞介素-1β（IL-1β）诱导的环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）的表达及活性的药理作用。与未处理的对照相比，用IL-1β（5 ng/ml）刺激人软骨细胞24小时导致一氧化氮（NO）和前列腺素E2（PGE2）的产生显著增加（p<.001）。用EGCG预处理人软骨细胞显示，NO和PGE2的产生分别有48%和24%的剂量依赖性抑制，并且与iNOS和COX-2活性的抑制相关（p<.005）。此外，在经EGCG预处理的人软骨细胞中，IL-1β诱导的iNOS和COX-2的表达也受到显著抑制（p<.001）。与这些发现平行的是，EGCG也抑制了软骨细胞培养物中IL-1β诱导的乳酸脱氢酶（LDH）释放。总体而言，该研究表明，EGCG通过调节人软骨细胞中分解代谢介质NO和PGE2各自酶的表达和催化活性，提供针对IL-1β诱导产生这些介质的保护作用。此外，我们的结果还表明，EGCG在抑制关节炎关节中的软骨吸收方面可能具有潜在的治疗价值。
