Ursolic Acid Suppresses Interleukin-17 (IL-17) Production by Selectively Antagonizing the Function of RORλt Protein
Ursolic Acid Suppresses Interleukin-17 (IL-17) Production by Selectively Antagonizing the Function of RORλt Protein
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DOI：
10.1074/jbc.c111.250407
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发表时间：
2011-07-01
影响因子：
4.8
通讯作者：
Dong, Chen
中科院分区：
文献类型：
--
作者：
Xu, Tao;Wang, Xiaohu;Dong, Chen
Th 17细胞最近通过产生促炎细胞因子IL-17、IL-17 F和IL-22而成为炎性和自身免疫性疾病的主要参与者。Th 17细胞的分化和相关细胞因子的产生直接受ROR γ t控制。在这里，我们表明，熊果酸（UA），一种存在于草药中的小分子，选择性地和有效地抑制ROR γ t的功能，从而大大降低IL-17在发育和分化的Th 17细胞中的表达。此外，UA治疗可改善实验性自身免疫性脑脊髓炎。因此，结果表明UA作为有价值的候选药物或用于开发Th 17介导的炎性疾病和癌症的治疗的领先化合物。
Th17 cells have recently emerged as a major player in inflammatory and autoimmune diseases via the production of pro-inflammatory cytokines IL-17, IL-17F, and IL-22. The differentiation of Th17 cells and the associated cytokine production is directly controlled by ROR gamma t. Here we show that ursolic acid (UA), a small molecule present in herbal medicine, selectively and effectively inhibits the function of ROR gamma t, resulting in greatly decreased IL-17 expression in both developing and differentiated Th17 cells. In addition, treatment with UA ameliorated experimental autoimmune encephalomyelitis. The results thus suggest UA as a valuable drug candidate or leading compound for developing treatments of Th17-mediated inflammatory diseases and cancer.