Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol
Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol
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DOI：
10.1002/art.1780400120
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发表时间：
1997-01-01
影响因子：
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通讯作者：
Tarkowski, A
中科院分区：
文献类型：
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作者：
Josefsson, E;Tarkowski, A
Objective.评价雌二醇的内源性代谢产物2-甲氧基雌二醇对DBA/1小鼠II型胶原诱导的关节炎（CIA）的抗关节炎作用。临床和组织学评价了2-甲氧乙烯醚治疗对CIA发展的影响。采用标准方法分析2-甲氧基乙烯对淋巴细胞和内皮细胞增殖和分化的体外影响。2-甲氧乙烯醚能显著抑制CIA的发生。与2-甲氧基乙烯醇孵育抑制了内皮细胞的体外增殖，表明该化合物下调血管生成。内皮细胞产生的一氧化氮（NO）也下调2-甲氧基乙烯。与雌二醇相反，2-甲氧基雌二醇既不对性器官产生可检测的雌性化作用，也不抑制造血器官中的白细胞发育。CIA的发展受到2-甲氧基乙烯的抑制，可能是通过抑制血管生成。减少NO的产生在体内可能是重要的，因为它是一种有效的促炎介质。由于与雌二醇相比，2-甲氧基雌二醇仅产生轻微的副作用，因此它是用于炎性疾病的治疗用途的令人感兴趣的候选者。
Objective. To evaluate the antiarthritic properties of 2-methoxyestradiol, an endogenous metabolite of estradiol, on type II collagen-induced arthritis (CIA) in DBA/1 mice.Methods. The effects of treatment with 2-methoxyestradiol on the development of CIA were evaluated clinically and histologically. The in vitro effects of 2-methoxyestradiol on lymphocyte and endothelial cell proliferation and differentiation were analyzed by standard methods.Results. The development of CIA was significantly suppressed by 2-methoxyestradiol. Incubation with 2-methoxyestradiol suppressed the in vitro proliferation of endothelial cells, indicating that this compound down-regulates angiogenesis. Endothelial cell production of nitric oxide (NO) was also down-regulated by 2-methoxyestradiol. In contrast to estradiol, 2-methoxyestradiol exerted neither detectable feminizing effects on the sex organs nor inhibition of leukocyte development in hematopoietic organs.Conclusion. The development of CIA is suppressed by 2-methoxyestradiol, possibly via inhibition of angiogenesis. Diminished NO production could be of importance in vivo because it is a potent proinflammatory mediator. Since 2-methoxyestradiol exerts only mild side effects compared with estradiol, it is an interesting candidate for therapeutic use in inflammatory diseases.