Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in mice.
Front Immunol
; 14: 1182278, 2023.
Article
em En
| MEDLINE
| ID: mdl-37234175
ABSTRACT
Objective:
Despite intensive research on rheumatoid arthritis, the pathomechanism of the disease is still not fully understood and the treatment has not been completely resolved. Previously we demonstrated that the GTPase-activating protein, ARHGAP25 has a crucial role in the regulation of basic phagocyte functions. Here we investigate the role of ARHGAP25 in the complex inflammatory process of autoantibody-induced arthritis.Methods:
Wild-type and ARHGAP25 deficient (KO) mice on a C57BL/6 background, as well as bone marrow chimeric mice, were treated i.p. with the K/BxN arthritogenic or control serum, and the severity of inflammation and pain-related behavior was measured. Histology was prepared, leukocyte infiltration, cytokine production, myeloperoxidase activity, and superoxide production were determined, and comprehensive western blot analysis was conducted.Results:
In the absence of ARHGAP25, the severity of inflammation, joint destruction, and mechanical hyperalgesia significantly decreased, similarly to phagocyte infiltration, IL-1ß, and MIP-2 levels in the tibiotarsal joint, whereas superoxide production or myeloperoxidase activity was unchanged. We observed a significantly mitigated phenotype in KO bone marrow chimeras as well. In addition, fibroblast-like synoviocytes showed comparable expression of ARHGAP25 to neutrophils. Significantly reduced ERK1/2, MAPK, and I-κB protein signals were detected in the arthritic KO mouse ankles.Conclusion:
Our findings suggest that ARHGAP25 has a key role in the pathomechanism of autoantibody-induced arthritis in which it regulates inflammation via the I-κB/NF-κB/IL-1ß axis with the involvement of both immune cells and fibroblast-like synoviocytes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Superóxidos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Hungria