Neuroimmunology Unit, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada.
J Neuroimmunol. 2011 Jan;230(1-2):10-6. doi: 10.1016/j.jneuroim.2010.08.006. Epub 2010 Sep 9.
Human microglia, monocyte-derived dendritic cells (DCs) and macrophages ex vivo express relatively higher levels of sphingosine-1-phosphate (S1P) receptor 1 (S1P1) mRNA as compared to other receptor subtypes. The S1P agonist FTY720 decreased ERK phosphorylation and induced myosin light chain (MLC) II phosphorylation only in macrophages and DCs. FTY720 inhibited IL-12p70 production (CD40L induced) by DCs and macrophages but not microglia (poly I:C induced). IL-10 production was increased in DCs and unaffected in other myeloid cells. Despite similar receptor expression patterns, the distinct myeloid cell populations present in the human CNS, under steady-state or inflammatory conditions, exhibit differential responses to FTY720.
人源小胶质细胞、单核细胞衍生的树突状细胞（DC）和巨噬细胞在体外表达相对较高水平的鞘氨醇-1-磷酸（S1P）受体 1（S1P1）mRNA，与其他受体亚型相比。S1P 激动剂 FTY720 仅在巨噬细胞和 DC 中降低 ERK 磷酸化并诱导肌球蛋白轻链（MLC）II 磷酸化。FTY720 抑制 DC 和巨噬细胞（CD40L 诱导）但不抑制小胶质细胞（poly I:C 诱导）产生 IL-12p70。IL-10 的产生在 DC 中增加，而在其他髓样细胞中不受影响。尽管存在相似的受体表达模式，但在稳态或炎症条件下存在于人中枢神经系统中的不同髓样细胞群对 FTY720 表现出不同的反应。
