Thioredoxin protects against joint destruction in a murine arthritis model.
Thioredoxin protects against joint destruction in a murine arthritis model.
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DOI：
10.1016/j.freeradbiomed.2006.01.006
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发表时间：
2006-05
影响因子：
7.4
通讯作者：
G. Tsuji;M. Koshiba;Hajime Nakamura;Hidekazu Kosaka;S. Hatachi;Chiyo Kurimoto;M. Kurosaka;Y. Hayashi;J. Yodoi;S. Kumagai
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文献类型：
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作者：
G. Tsuji;M. Koshiba;Hajime Nakamura;Hidekazu Kosaka;S. Hatachi;Chiyo Kurimoto;M. Kurosaka;Y. Hayashi;J. Yodoi;S. Kumagai
硫氧还蛋白（TRX）是一种氧化应激诱导的生物抗氧化剂，在类风湿关节炎（RA）患者的滑膜细胞中高度表达。有很多证据表明，氧化应激在RA关节的炎症和破坏中起着关键作用;然而，TRX和RA之间的功能关系仍然未知。因此，我们研究了TRX在RA的炎症和关节损伤过程中发挥的作用，使用小鼠模型，其中关节炎是通过给予抗II型胶原单克隆抗体（mAb）和脂多糖（LPS）的混合物诱导的。在Wt小鼠中，mAb/LPS注射诱导关节内的中性粒细胞浸润、软骨破坏和软骨细胞凋亡，所有这些在TRX转基因（TRX-Tg）小鼠中均被显著抑制。此外，TRX-Tg小鼠注射mAb/LPS后，在Wt小鼠中观察到的8-羟基-2 ′-脱氧鸟苷（8-OHdG）表达几乎完全被抑制。重组TRX的施用也抑制mAb/LPS诱导的Wt小鼠关节肿胀。总之，这些结果表明，TRX可以预防关节炎，并且是开发治疗RA的新疗法的合理候选者。
Thioredoxin (TRX) is an oxidative stress-inducible biological antioxidant that is highly expressed in the synoviocytes of rheumatoid arthritis (RA) patients. There is much evidence that oxidative stress plays a key role in the inflammation and destruction of RA joints; the functional relationship between TRX and RA remains unknown, however. We therefore investigated the role played by TRX in the inflammatory and joint-damaging processes of RA using a murine model in which arthritis was induced by administering a mixture of anti-type II collagen monoclonal antibodies (mAb) and lipopolysaccharide (LPS). In Wt mice mAb/LPS injection induced neutrophil infiltration, cartilage destruction, and chondrocyte apoptosis within the joints, all of which were dramatically suppressed in TRX transgenic (TRX-Tg) mice. Moreover, the 8-hydoxy-2′-deoxyguanosine (8-OHdG) expression seen in Wt mice after mAb/LPS injection was almost completely inhibited in TRX-Tg mice. The administration of recombinant TRX also suppressed mAb/LPS-induced joint swelling in Wt mice. Taken together, these results suggest that TRX protects against arthritis and is a plausible candidate with which to develop novel therapies for the treatment of RA.