| First Author | Czárán D | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1182278 | PubMed ID | 37234175 |
| Mgi Jnum | J:336758 | Mgi Id | MGI:7484990 |
| Doi | 10.3389/fimmu.2023.1182278 | Citation | Czaran D, et al. (2023) Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in mice. Front Immunol 14:1182278 |
| abstractText | 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-1beta, 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-kappaB 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-kappaB/NF-kappaB/IL-1beta axis with the involvement of both immune cells and fibroblast-like synoviocytes. |
