Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis
Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis
复制标题
DOI：
10.1016/j.clim.2005.11.012
复制
发表时间：
2006-06-01
影响因子：
8.6
通讯作者：
Funauchi, Masanori
中科院分区：
文献类型：
--
作者：
Nozaki, Yuji;Yamagata, Toshiaki;Funauchi, Masanori
目的：为探讨全反式维甲酸（ATRA）对胶原诱导性关节炎（CIA）DBA/1 J小鼠关节破坏的改善作用及细胞因子的影响，从注射II型胶原开始，DBA/1 J小鼠腹腔注射PBS或ATRA 0.5mg，每周3次，共35 d。通过测定关节炎和组织学评分以及测量细胞增殖、细胞因子产生来监测治疗效果IL-2、IL-10、IL-12、IL-6、IFN-γ和TNF-α）和IgG，以及诱导型一氧化氮合酶（iNOS）、单核细胞趋化蛋白-1（MCP-1）和CXCR 3的mRNA表达。ATRA治疗组小鼠关节炎评分和关节炎发生率均低于PBS治疗组。与PBS治疗组相比，ATRA治疗组小鼠关节损伤的组织学证据降低了34%，巨噬细胞浸润减少。II型胶原和ConA刺激的脾细胞增殖，细胞因子的产生与PBS处理的小鼠相比，ATRA处理的小鼠中IL-6、IL-12和TNF-α的水平、总IgG和IgG 1抗胶原抗体的血清水平以及MCP-1的mRNA表达显著降低。全反式维甲酸改善了临床进程，并减少了小鼠CIA中炎性细胞因子、免疫球蛋白和趋化因子的产生。这些数据表明，全反式维甲酸也可能是有效的治疗炎症性关节炎，如人类类风湿性关节炎。(c)2005年爱思唯尔公司All rights reserved.
Objective: To determine whether all-trans-retinoic acid (ATRA) improves the destruction of joints and the effect of cytokines on DBA/1J mice with collagen-induced arthritis (CIA).Methods: Starting from the time of type II collagen injection, DBA/1J mice were injected intraperitoneally with PBS or 0.5 mg of ATRA 3 times per week for 35 days. The effects of treatment were monitored by determining arthritis and histological scores and measuring cellular proliferation, production of cytokines (IL-2, IL-10, IL-12, IL-6, IFN-gamma, and TNF-alpha) and IgG, and the expression of mRNAs for inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), and CXCR3.Results: The arthritis score and incidence of arthritis were lower in the mice treated with ATRA than in those treated with PBS. Histopathologic evidence of joint damage was 34% lower, and the infiltrations of macrophages were reduced in the mice treated with ATRA compared with those treated with PBS. Type II collagen- and ConA-stimutated proliferation of spleen cells, the production of cytokines (IL-6, IL-12, and TNF-alpha), the serum levels of total IgG and IgG1 anti-collagen antibodies, and the expression of mRNAs for MCP-1 were significantly reduced in the mice treated with ATRA than in those treated with PBS.Conclusion: ATRA improved the clinical course and reduced the production of inflammatory cytokines, immunoglobulin, and chemokines in murine CIA. These data suggest that ATRA might be also effective for the treatment of inflammatory arthritis like human rheumatoid arthritis. (c) 2005 Elsevier Inc. All rights reserved.