Beneficial effects of a polyamine biosynthesis inhibitor on lupus in MRL-lpr/lpr mice.
Beneficial effects of a polyamine biosynthesis inhibitor on lupus in MRL-lpr/lpr mice.
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DOI：
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发表时间：
1989
影响因子：
4.6
通讯作者：
T. Thomas;R. Messner
中科院分区：
文献类型：
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作者：
T. Thomas;R. Messner
二氟甲基鸟氨酸 (DFMO) 是一种实验药物，可灭活鸟氨酸脱羧酶，从而减少多胺的产生，对雌性 MRL-lpr/lpr 小鼠的平均生存时间以及小鼠狼疮的临床和实验室表现有有益的影响。与相同品系的年龄和性别匹配的对照小鼠相比，DFMO 治疗的小鼠的平均生存时间增加了 29%。未经治疗的小鼠在 14 周龄时淋巴结肿大很明显，但在 DFMO 治疗的小鼠中延迟到 19 周龄。此外，与未处理的小鼠相比，DFMO处理的小鼠血清中抗DNA抗体的浓度显着降低。这些结果开启了开发基于多胺生物合成抑制剂的新型治疗剂用于治疗人类自身免疫性疾病的可能性。 DFMO 的可能作用机制包括其对细胞增殖的抑制作用以及其防止 DNA 呈现免疫原性左手 Z-DNA 构象的能力。
Difluoromethylornithine (DFMO), an experimental drug that inactivates ornithine decarboxylase and thus reduces the production of polyamines has a beneficial effect on the mean survival time and the clinical and laboratory manifestations of murine lupus in female MRL-lpr/lpr mice. DFMO-treated mice showed a 29% increase in the mean survival time compared with age- and sex-matched control mice of the same strain. Lymphadenopathy was evident in untreated mice at 14 weeks of age, but was delayed until 19 weeks of age in DFMO-treated mice. In addition, the sera of DFMO-treated mice contained a significantly lower concentration of anti-DNA antibodies compared with untreated mice. These results open the possibility of development of a new class of therapeutic agents based on polyamine biosynthesis inhibitors for the treatment of human autoimmune disease. Possible mechanisms for the action of DFMO include its inhibitory action on cell proliferation as well as its ability to prevent DNA from assuming an immunogenic left-handed Z-DNA conformation.