Low dose IL‐2 suppress osteoclastogenesis in collagen‐induced arthritis via JNK dependent pathway

Abstract

Abstract Background Rheumatoid arthritis (RA) is one of the most common chronic immune joint diseases, mainly involving blood vessels and small joints. The complex pathogenesis of RA greatly increases the difficulty of treatment. At present, the common hormone and immunosuppressive therapy are not effective, while low‐dose interleukin‐2 (IL‐2) recently has been found to possess some advantages for immunotherapy. However, its related signal pathway remains to be elucidated. Methods We fabricated the model of arthritis in mice, and then low‐dose IL‐2 was injected at a fixed time point to observe the changes of related vascular and organ pathology, inflammatory factors, and signal pathway proteins, which were verified by statistical analysis. Results Low dose IL‐2 can reduce the severity of vascular and bone lesions in collagen‐induced arthritis immune model, and inhibit osteoclast formation in vitro by phosphorylation of nuclear factor‐κB (NF‐κB), which inhibits the receptor activator of NF‐κB ligand effect through c‐Jun N‐terminal kinase (JNK) pathway, and its immunotherapeutic effect depends on the activation of JNK. Conclusion It is the first time for us to prove that low dose IL‐2 can inhibit osteoclast formation in collagen‐induced arthritis through the JNK dependent pathway, which will provide the angle and theoretical basis for future immunotherapy of IL‐2.

Keywords

• c‐Jun N‐terminal kinase
• collagen‐induced arthritis
• interleukin‐2
• NF‐κB
• rheumatoid arthritis