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Exosome-mediated delivery of super-repressor IκBα alleviates inflammation and joint damages in rheumatoid arthritis.
Lee, Hae-In; Ahn, Min-Joo; Yoo, Jae-Kwang; Ahn, So-Hee; Park, Seon Young; Seo, Hyangmi; Kim, Moon-Ju; Lee, Yu Jeong; Jang, Hyun Hee; Shim, Seung Cheol; Won, Eun Jeong; Park, Cheolhyoung; Choi, Chulhee; Kim, Tae-Jong.
Afiliación
  • Lee HI; Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, 501-757, Republic of Korea.
  • Ahn MJ; Department of Biomedical Sciences, Graduate School of Chonnam National University, Gwangju, Republic of Korea.
  • Yoo JK; Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, Republic of Korea.
  • Ahn SH; ILIAS Biologics Inc, Daejeon, Republic of Korea.
  • Park SY; ILIAS Biologics Inc, Daejeon, Republic of Korea.
  • Seo H; ILIAS Biologics Inc, Daejeon, Republic of Korea.
  • Kim MJ; ILIAS Biologics Inc, Daejeon, Republic of Korea.
  • Lee YJ; Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, 501-757, Republic of Korea.
  • Jang HH; Department of Biomedical Sciences, Graduate School of Chonnam National University, Gwangju, Republic of Korea.
  • Shim SC; Department of Biomedical Sciences, Graduate School of Chonnam National University, Gwangju, Republic of Korea.
  • Won EJ; Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, Republic of Korea.
  • Park C; Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Choi C; ILIAS Biologics Inc, Daejeon, Republic of Korea.
  • Kim TJ; ILIAS Biologics Inc, Daejeon, Republic of Korea. cchoi@iliasbio.com.
Arthritis Res Ther ; 26(1): 2, 2024 01 02.
Article en En | MEDLINE | ID: mdl-38167497
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Exosomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Exosomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido