Related Experiment Video
Updated: Jul 21, 2025
07:37
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
199
Nrf2 activation improves experimental rheumatoid arthritis.
Anqi Zhang1, Takafumi Suzuki1, Saki Adachi2
1Departments of Biochemistry and Molecular Biology, Tohoku Medical-Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Departments of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
Free Radical Biology & Medicine
|July 26, 2023
Summary
Activating Nrf2 (Nuclear factor erythroid 2-related factor 2) effectively treats rheumatoid arthritis in mice. This approach reduces inflammation and boosts antioxidant defenses, offering a promising new therapeutic strategy for the disease.
Area of Science:
- Immunology
- Autoimmune Diseases
- Molecular Biology
Background:
- Rheumatoid arthritis is a systemic autoimmune disease causing joint pain and dysfunction.
- Current treatments for rheumatoid arthritis carry risks of serious adverse effects.
- There is a need for novel therapeutic strategies with improved safety profiles.
Purpose of the Study:
- To investigate the therapeutic potential of Nuclear factor erythroid 2-related factor 2 (Nrf2) activation in a mouse model of rheumatoid arthritis.
- To determine the mechanisms by which Nrf2 activation impacts inflammatory and oxidative stress pathways in arthritis.
Main Methods:
- Utilized SKG mice, which develop T cell-mediated autoimmune arthritis after zymosan A injection.
- Employed genetic Nrf2 activation via Kelch-like ECH-associated protein 1 (Keap1) knockdown.
- Administered CDDO-Im, a chemical Nrf2 inducer, to assess its preventive and therapeutic effects.
- Analyzed gene expression of pro-inflammatory cytokines and antioxidant enzymes in isolated fibroblast-like synoviocytes (FLS).
Main Results:
- Genetic Nrf2 activation by Keap1 knockdown significantly repressed arthritis in SKG mice.
- Nrf2 activation inhibited pro-inflammatory cytokine expression and induced antioxidant enzyme expression.
- Oral administration of CDDO-Im demonstrated both preventive and therapeutic effects on arthritis in an Nrf2-dependent manner.
- Nrf2 activation in fibroblast-like synoviocytes led to decreased pro-inflammatory cytokine and increased antioxidant enzyme gene expression.
Conclusions:
- Nrf2 activation exerts significant anti-arthritis effects in the SKG experimental rheumatoid arthritis model.
- Targeting Nrf2 represents a promising novel therapeutic strategy for rheumatoid arthritis.
- The findings highlight the role of Nrf2 in modulating inflammatory and oxidative pathways relevant to rheumatoid arthritis pathogenesis.
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