Thioredoxin protects against joint destruction in a murine arthritis model

被引:27
|
作者
Tsuji, Goh
Koshiba, Masahiro
Nakamura, Hajime
Kosaka, Hidekazu
Hatachi, Saori
Kurimoto, Chiyo
Kurosaka, Masahiro
Hayashi, Yoshitake
Yodoi, Junji
Kumagai, Shunichi
机构
[1] Kobe Univ, Grad Sch Med, Dept Clin Pathol & Immunol, Chuo Ku, Kobe, Hyogo 6500017, Japan
[2] Kobe Univ, Grad Sch Med, Dept Evidence Based Lab Med Sysmex, Kobe, Hyogo 6500017, Japan
[3] Kyoto Univ Hosp, Translat Res Ctr, Kyoto 606, Japan
[4] Kobe Univ, Grad Sch Med, Dept Orthopaed Surg, Kobe, Hyogo 6500017, Japan
[5] Kobe Univ, Grad Sch Med, Int Ctr Med Res & Treatment, Div Mol Med & Med Genet, Kobe, Hyogo 6500017, Japan
[6] Kyoto Univ, Inst Virus Res, Kyoto 606, Japan
基金
日本学术振兴会;
关键词
thioredoxin; rheumatoid arthritis; animal model; oxidative stress; antioxidants; free radical;
D O I
10.1016/j.freeradbiomed.2006.01.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 rnAb/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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:1721 / 1731
页数:11
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