Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells.
Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells.
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DOI：
10.1016/j.fob.2015.06.001
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发表时间：
2015
期刊：
影响因子：
2.6
通讯作者：
Fukuda, Kanji
中科院分区：
文献类型：
--
作者：
Onodera, Yuta;Teramura, Takeshi;Takehara, Toshiyuki;Shigi, Kanae;Fukuda, Kanji
关节炎关节中的氧化应激参与炎症介质的产生。氧化应激诱导的 Cox-2 表达由 MAPK 和 NF-κB 介导。 ROS 诱导的 MAPK 和 NF-κB 通过抑制 MAPKKK TAK1 而减弱。抑制 TAK1 活性导致 Cox-2 和 PGE2 表达减少。 ROS 诱导的 TAK1 激活和 Cox-2 表达被抗氧化剂 N-乙酰半胱胺和透明质酸抑制。关节炎关节内的氧化应激已被证明参与产生组织变性和炎症介质。 COX-2 是炎症组织中炎症作用、疼痛和一些分解代谢反应的介质。在这里，我们证明了牛滑膜成纤维细胞中氧化应激与 Cox-2 表达之间的直接关系。此外，我们阐明了一种新机制，其中氧化应激通过 TAK1 激活诱导 MAPK 和 NF-κB 磷酸化，并导致 Cox-2 和前列腺素 E2 表达增加。最后，我们证明在体外和体内补充 N-乙酰半胱胺和透明质酸等抗氧化剂可以抑制 ROS 诱导的 Cox-2 表达。从这些结果中，我们得出结论，氧化应激是滑膜成纤维细胞生成 Cox-2 的重要因素，因此中和它可能是慢性关节疾病姑息治疗的有效策略。
Oxidative stress in the arthritis joint is involved in generating mediators for inflammation. Oxidative stress-induced expression of Cox-2 was mediated by MAPKs and NF-κB. ROS-induced MAPKs and NF-κB were attenuated by inhibition of MAPKKK TAK1. Inhibition of TAK1 activity resulted in reduced expression of Cox-2 and PGE2. ROS-induced TAK1 activation and Cox-2 expression was inhibited by antioxidants N-acetyl cysteamine and hyaluronic acid. Oxidative stress within the arthritis joint has been indicated to be involved in generating mediators for tissue degeneration and inflammation. COX-2 is a mediator in inflammatory action, pain and some catabolic reactions in inflamed tissues. Here, we demonstrated a direct relationship between oxidative stress and Cox-2 expression in the bovine synovial fibroblasts. Furthermore, we elucidated a novel mechanism, in which oxidative stress induced phosphorylation of MAPKs and NF-κB through TAK1 activation and resulted in increased Cox-2 and prostaglandin E2 expression. Finally, we demonstrated that ROS-induced Cox-2 expression was inhibited by supplementation of an antioxidant such as N-acetyl cysteamine and hyaluronic acid in vitro and in vivo. From these results, we conclude that oxidative stress is an important factor for generation of Cox-2 in synovial fibroblasts and thus its neutralization may be an effective strategy in palliative therapy for chronic joint diseases.
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