富马酸二甲酯通过 HCA/GPR109A 通路下调免疫应答：对多发性硬化症治疗的意义。
Dimethyl fumarate downregulates the immune response through the HCA/GPR109A pathway: Implications for the treatment of multiple sclerosis.
机构信息
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil.
Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil; CATEM- Center for Multiple Sclerosis Care, Santa Casa de São Paulo, São Paulo, Brazil..
出版信息
Mult Scler Relat Disord. 2018 Jul;23:46-50. doi: 10.1016/j.msard.2018.04.016. Epub 2018 Apr 25.
BACKGROUND
The mechanisms of action of dimethyl fumarate (DMF), and its metabolite, monomethyl fumarate (MMF), for the treatment of multiple sclerosis are not completely elucidated.
OBJECTIVES
To discuss the role of DMF/MMF-induced hydroxycarboxylic acid receptor 2 (HCA/GPR109A) pathway activation in the immune response and treatment of MS.
METHODS
A narrative (traditional) review of the current literature.
RESULTS
Studies have shown that binding of DMF/MMF to HCA on dendritic cells inhibits the production of pro-inflammatory cytokines in vitro and in MS murine models. Evidence suggests that activation of HCA expressed in immune cells and gut epithelial cells by DMF/MMF, may induce anti-inflammatory responses in the intestinal mucosa.
CONCLUSION
Although the DMF/MMF mechanism of action remains unclear, evidence suggests that the activation of HCA/GPR109A pathway downregulates the immune response and may activate anti-inflammatory response in the intestinal mucosa, possibly leading to reduction in CNS tissue damage in MS patients.
背景
二甲基富马酸（DMF）及其代谢产物单甲基富马酸（MMF）治疗多发性硬化症的作用机制尚未完全阐明。
目的
讨论 DMF/MMF 诱导的羟羧酸受体 2（HCA/GPR109A）通路激活在免疫反应和 MS 治疗中的作用。
方法
对当前文献进行叙述性（传统）综述。
结果
研究表明，DMF/MMF 与树突状细胞上的 HCA 结合可抑制体外和 MS 鼠模型中促炎细胞因子的产生。有证据表明，DMF/MMF 激活免疫细胞和肠道上皮细胞中表达的 HCA，可能在肠道黏膜中诱导抗炎反应。
结论
尽管 DMF/MMF 的作用机制尚不清楚，但有证据表明 HCA/GPR109A 通路的激活可下调免疫反应，并可能在肠道黏膜中激活抗炎反应，从而减少 MS 患者中枢神经系统组织损伤。
Zotero 插件