Thioredoxin protects against joint destruction in a murine arthritis model.
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.
Tsuji
Goh
G
Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, 7-5-1 Kobe 650-0017, Japan.
Koshiba
Masahiro
M
Nakamura
Hajime
H
Kosaka
Hidekazu
H
Hatachi
Saori
S
Kurimoto
Chiyo
C
Kurosaka
Masahiro
M
Hayashi
Yoshitake
Y
Yodoi
Junji
J
Kumagai
Shunichi
S