Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
Department of Anesthesiology and Pain Medicine, College of Medicine, Dong-A University, Busan, Republic of Korea.
Int Immunopharmacol. 2014 May;20(1):269-75. doi: 10.1016/j.intimp.2014.03.005. Epub 2014 Mar 19.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Gallium nitrate has been reported to reserve immunosuppressive activities. Therefore, we assessed the therapeutic effects of gallium nitrate in the mouse model of developed type II collagen-induced arthritis (CIA). CIA was induced by bovine type II collagen with Complete Freund's adjuvant. CIA mice were intraperitoneally treated from day 36 to day 49 after immunization with 3.5mg/kg/day, 7mg/kg/day gallium nitrate or vehicle. Gallium nitrate ameliorated the progression of mice with CIA. The clinical symptoms of collagen-induced arthritis did not progress after treatment with gallium nitrate. Gallium nitrate inhibited the increase of CD4(+) T cell populations (p<0.05) and also inhibited the type II collagen-specific IgG2a-isotype autoantibodies (p<0.05). Gallium nitrate reduced the serum levels of TNF-α, IL-6 and IFN-γ (p<0.05) and the mRNA expression levels of these cytokine and MMPs (MMP2 and MMP9) in joint tissues. Western blotting of members of the NF-κB signaling pathway revealed that gallium nitrate inhibits the activation of NF-κB by blocking IκB degradation. These data suggest that gallium nitrate is a potential therapeutic agent for autoimmune inflammatory arthritis through its inhibition of the NF-κB pathway, and these results may help to elucidate gallium nitrate-mediated mechanisms of immunosuppression in patients with RA.
类风湿关节炎（RA）是一种慢性自身免疫性炎症性疾病。硝酸镓已被报道具有免疫抑制活性。因此，我们评估了硝酸镓在已建立的 II 型胶原蛋白诱导关节炎（CIA）小鼠模型中的治疗效果。CIA 通过牛 II 型胶原蛋白和完全弗氏佐剂诱导。CIA 小鼠在免疫后第 36 天至第 49 天每天经腹腔给予 3.5mg/kg/天、7mg/kg/天的硝酸镓或载体。硝酸镓改善了 CIA 小鼠的进展。用硝酸镓治疗后，胶原诱导关节炎的临床症状没有进展。硝酸镓抑制 CD4(+)T 细胞群的增加（p<0.05），并抑制 II 型胶原蛋白特异性 IgG2a-同种型自身抗体（p<0.05）。硝酸镓降低了 TNF-α、IL-6 和 IFN-γ 的血清水平（p<0.05）以及关节组织中这些细胞因子和 MMPs（MMP2 和 MMP9）的 mRNA 表达水平。NF-κB 信号通路成员的 Western 印迹分析表明，硝酸镓通过阻止 IκB 降解来抑制 NF-κB 的激活。这些数据表明，硝酸镓通过抑制 NF-κB 通路成为自身免疫性炎症性关节炎的一种潜在治疗剂，这些结果可能有助于阐明硝酸镓在 RA 患者中介导免疫抑制的机制。
