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Open Access 26-02-2024 | Sulfasalazine | Original Article

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

Authors: Chenyu Zhao, Yunyuan Yu, Guangrong Yin, Chao Xu, Jiahao Wang, Liangliang Wang, Gongyin Zhao, Su Ni, Haoxing Zhang, Baojun Zhou, Yuji Wang

Published in: Inflammopharmacology | Issue 2/2024

Abstract

Objective

Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA.

Methods

CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund’s adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining.

Results

The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53.

Conclusions

Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.

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Title: Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis
Authors: Chenyu Zhao
Yunyuan Yu
Guangrong Yin
Chao Xu
Jiahao Wang
Liangliang Wang
Gongyin Zhao
Su Ni
Haoxing Zhang
Baojun Zhou
Yuji Wang
Publication date: 26-02-2024
Publisher: Springer International Publishing
Keywords: Sulfasalazine
Rheumatoid Arthritis
Published in: Inflammopharmacology / Issue 2/2024
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-024-01439-6

At a glance: The STEP trials

Springer Medicine

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

Abstract

Objective

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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