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Exosome-mediated delivery of super-repressor IκBα alleviates inflammation and joint damages in rheumatoid arthritis

Authors :
Hae-In Lee
Min-Joo Ahn
Jae-Kwang Yoo
So-Hee Ahn
Seon Young Park
Hyangmi Seo
Moon-Ju Kim
Yu Jeong Lee
Hyun Hee Jang
Seung Cheol Shim
Eun Jeong Won
Cheolhyoung Park
Chulhee Choi
Tae-Jong Kim
Source :
Arthritis Research & Therapy, Vol 26, Iss 1, Pp 1-13 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Background This study aims to investigate the potential anti-inflammatory effects of exosomes engineered to carry super-repressor IκB (Exo-srIκB), an exosome-based NF-κB inhibitor, in the context of RA. Methods Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from patients diagnosed with RA and treated with Exo-srIκB to test the therapeutic potential. Flow cytometry analysis was performed to assess the production of inflammatory cytokines (IL-17A and GM-CSF) by the cells. ELISA was utilized to measure the levels of TNF-α, IL-17A, IL-6, and GM-CSF. Arthritis was induced in SKG mice by intraperitoneal injection of curdlan. DBA/1 J mice were used in collagen-induced arthritis (CIA) experiments. After the development of arthritis, mice were injected with either Exo-Naïve (control exosome) or Exo-srIκB. Arthritis scores were recorded biweekly, and histological observations of the ankle joint were conducted using H&E and safranin-O staining. Additionally, bone erosion was evaluated using micro-CT imaging. Results In the ex vivo study involving human PBMCs and SFMCs, treatment with Exo-srIκB demonstrated a notable reduction in inflammatory cytokines. Furthermore, in both the SKG and CIA models, Exo-srIκB treatment exhibited significant reductions in inflammation, cartilage destruction, and bone erosion within the joint tissues when compared to the Exo-Naive control group. Additionally, the radiographic score assessed through microCT showed a significant decrease compared to the Exo-Naive control group. Conclusion Overall, these findings suggest that Exo-srIκB possesses anti-inflammatory properties in human RA cells and animal models, making it a promising therapeutic candidate for the treatment of RA.

Details

Language :
English
ISSN :
14786362
Volume :
26
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Arthritis Research & Therapy
Publication Type :
Academic Journal
Accession number :
edsdoj.6e90f45f841845ca8162079ca99c48fa
Document Type :
article
Full Text :
https://doi.org/10.1186/s13075-023-03225-1