Abstract
This study aimed to evaluate the possible role of heat shock protein-70 (HSP70) induction by 17-allylaminodemethoxygeldanamycin (17-AAG) in collagen-induced arthritis in rats. Male Wistar rats were divided into five groups (n = 10/group) and were treated intraperitoneally twice a week for 4 weeks, namely normal control (saline), arthritis control (AR; saline), AR + 17-AAG, AR + methotrexate (MTX), and AR + 17-AAG + MTX. At the end of the treatments, arthritic score was determined and then the animals were sacrificed. Erythrocyte sedimentation rate (ESR), serum levels of HSP70, interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), rheumatic factor (RF), C-reactive protein (CRP), malondialdehyde (MDA), glutathione peroxidase (GPx), and matrix metalloproteinase-9 (MMP-9) were determined. In the AR group, all parameters increased significantly, except for GPx, which showed a pronounced decrease. The 17-AAG and/or MTX treatments significantly reduced arthritic score, ESR, IL-17, TNF-α, RF, CRP, MDA, and MMP-9 with significant increase in GPx compared to the AR group. The HSP70 level was significantly higher in the AR + 17-AAG and the AR + 17-AAG + MTX groups but significantly lower in the AR + MTX group as compared to the AR group. Also, it was significantly lower in the AR + MTX group as compared to the AR + 17-AAG group. We concluded that HSP70 induction by 17-AAG attenuated the inflammatory process in a rheumatoid arthritis (RA) model induced by collagen, which suggested that HSP70 inducers can be promising agents in the treatment of RA.
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