What is it about?

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 weekly for 4 weeks, accordingly: 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, then animals were sacrificed. Erythrocyte sedimentation rate (ESR), serum levels of HSP70, interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-), rheumatic factor (RF), C-reactive protein (CRP), malondialdehyde (MDA), glutathione peroxidase (GPx) and matrix metalloproteinase-9 (MMP-9) were determined. In AR group, all of the parameters increased significantly, except GPx, which showed a pronounced decrease. 17-AAG and/or MTX treatments significantly reduced arthritic score, ESR, IL-17, TNF-, RF, CRP, MDA and MMP-9 with significant increase of GPx compared to AR group. As regard the HSP-70 level, it was significantly higher in AR+17-AAG and AR+17-AAG+MTX groups but significantly lower in AR+MTX group as compared to AR group. Also, it was significantly lower in AR+MTX group as compared to AR+17-AAG group.

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Why is it important?

Rheumatoid arthritis (RA) is an autoimmune systemic disease with chronic inflammatory character that results in morbidity and mortality. Methotrexate (MTX) is considered the standard anti-rheumatic drug due to its effectiveness in prolonged clinical use. However, its administration is limited due to its toxic adverse effects as it can cause serious infections, cytopenia, ulceration of mucous membranes and nausea. So, there is a need to use new anti-rheumatic drug or develop a new strategy in the treatment of RA in combination with MTX

Perspectives

17-AAG alone or in combination with low dose of MTX attenuated the RA in collagen induced arthritis model by its anti-inflammatory and anti-oxidant effects which might be due to induction of HSP70. Therefore, we suggest that HSP70 co-inducers may be promising agents in the treatment of RA, or its combination with low dose of MTX may have a therapeutic effect in the treatment of RA.

mervat elsaka
Tanta University Faculty of Medicine

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This page is a summary of: The possible role of heat shock protein-70 induction in collagen-induced arthritis in rats, Physiology International, July 2019, Akademiai Kiado,
DOI: 10.1556/2060.106.2019.17.
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