Inhibition of Synovial Hyperplasia, Rheumatoid T Cell Activation, and Experimental Arthritis in Mice by Sulforaphane, a Naturally Occurring Isothiocyanate
Inhibition of Synovial Hyperplasia, Rheumatoid T Cell Activation, and Experimental Arthritis in Mice by Sulforaphane, a Naturally Occurring Isothiocyanate
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DOI：
10.1002/art.25017
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发表时间：
2010-01-01
影响因子：
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通讯作者：
Kim, Wan-Uk
中科院分区：
文献类型：
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作者：
Kong, Jin-Sun;Yoo, Seung-Ah;Kim, Wan-Uk
目标。目的：探讨萝卜硫素（SFN）对类风湿关节炎（RA）滑膜细胞增生和T细胞活化的调节作用。MTT法测定滑膜细胞存活。Western blot检测Bcl-2、Bax、p53、pAkt水平。用酶联免疫吸附法分析单个核细胞培养上清中细胞因子的浓度。实验观察了SFN对实验性关节炎小鼠的体内作用。SFN通过调节Bcl-2/Bax、p53和pAkt的表达诱导滑膜细胞凋亡。此外，非凋亡剂量的SFN抑制T细胞增殖以及抗cd3抗体刺激的RA CD4+ T细胞产生白细胞介素-17 （IL-17）和肿瘤坏死因子α (TNF - α)。抗cd3抗体诱导的维甲酸相关孤儿受体γ t和t -bet的表达增加也被SFN抑制。此外，小鼠腹腔注射SFN可抑制II型胶原（CII）诱导的关节炎的临床严重程度、抗CII抗体水平和T细胞对CII的反应。经SFN处理后，这些小鼠的淋巴结细胞和脾脏细胞产生的IL-17、TNF α、IL-6和干扰素- γ明显减少。SFN对小鼠抗cii抗体诱导的关节炎也有一定的缓解作用。体外实验发现SFN可抑制类风湿T细胞滑膜增生、活化T细胞增殖以及IL-17和TNF α的产生。SFN的抗关节炎和免疫调节作用已在体内得到证实，这表明SFN可能是治疗RA的一种可能的选择。
Objective. To investigate whether sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables such as broccoli, regulates synoviocyte hyperplasia and T cell activation in rheumatoid arthritis (RA).Methods. Synoviocyte survival was assessed by MTT assay. The levels of Bcl-2, Bax, p53, and pAkt were determined by Western blot analysis. Cytokine concentrations in culture supernatants from mononuclear cells were analyzed by enzyme-linked immunosorbent assay. The in vivo effects of SFN were examined in mice with experimentally induced arthritis.Results. SFN induced synoviocyte apoptosis by modulating the expression of Bcl-2/Bax, p53, and pAkt. In addition, nonapoptotic doses of SFN inhibited T cell proliferation and the production of interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF alpha) by RA CD4+ T cells stimulated with anti-CD3 antibody. Anti-CD3 antibody-induced increases in the expression of retinoic acid-related orphan receptor gamma t and T-bet were also repressed by SFN. Moreover, the intraperitoneal administration of SFN to mice suppressed the clinical severity of arthritis induced by injection of type II collagen (CII), the anti-CII antibody levels, and the T cell responses to CII. The production of IL-17, TNF alpha, IL-6, and interferon-gamma by lymph node cells and spleen cells from these mice was markedly reduced by treatment with SFN. Anti-CII antibody-induced arthritis in mice was also alleviated by SFN injection.Conclusion. SFN was found to inhibit synovial hyperplasia, activated T cell proliferation, and the production of IL-17 and TNF alpha by rheumatoid T cells in vitro. The antiarthritic and immune regulatory effects of SFN, which were confirmed in vivo, suggest that SFN may offer a possible treatment option for RA.