Sulfatide, A Major Lipid Component of Myelin Sheath, Activates Inflammatory Responses as an Endogenous Stimulator in Brain-Resident Immune Cells
Sulfatide, A Major Lipid Component of Myelin Sheath, Activates Inflammatory Responses as an Endogenous Stimulator in Brain-Resident Immune Cells
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DOI：
10.4049/jimmunol.181.11.8077
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发表时间：
2008-12-01
影响因子：
4.4
通讯作者：
Park, Eun Jung
中科院分区：
文献类型：
--
作者：
Jeon, Sae-Bom;Yoon, Hee Jung;Park, Eun Jung
Sulfatide是髓鞘的主要脂质成分，参与中枢神经系统的多种细胞事件，其细胞水平最近被认为与许多炎症相关的神经元疾病有关。在此，我们报告单独的硫脂脂可以引发神经胶质，脑驻留免疫细胞的病理性炎症反应。我们发现，硫脂能改变原代小胶质细胞的形态，使其变为活化形态，并显著诱导原代小胶质细胞和星形胶质细胞产生多种炎症介质。此外，硫脂能在30分钟内迅速触发p38、ERK和JNK的磷酸化，并显著增强NF对NF-kappa B和AP-1结合元件的结合活性。然而，髓磷脂的另一主要脂质成分——非硫酸半乳糖脑苷对胶质细胞的激活没有影响。我们进一步发现，CD1d并没有促进硫脂脂刺激的MAPKs激活，尽管它的表达被硫脂脂增强，而硫脂脂处理的小胶质细胞实际上刺激了II型NKT细胞。硫脂能显著刺激cd1缺陷小鼠胶质细胞中MAPKs的磷酸化，磷酸化水平与野生型小鼠相似。磺胺脂引发的炎症事件似乎至少部分是通过l -选择素依赖机制发生的。l -选择素在暴露于硫脂后显著下调，抑制l -选择素导致硫脂引发的反应受到抑制。综上所述，这些结果表明脱髓鞘区域异常释放的硫脂可能在脑免疫系统中充当内源性刺激物，从而引起并进一步加剧脑病理状况。免疫学杂志，2008,18(1):8077-8087。
Sulfatide, a major lipid component of myelin sheath, participates in diverse cellular events of the CNS, and its cellular level has recently been implicated in many inflammation-associated neuronal diseases. Herein, we report that sulfatide alone can trigger pathological inflammatory responses in glia, brain-resident immune cells. We show that sulfatide changed the morphology of primary microglia to their activated form, and it significantly induced the production of various inflammatory mediators in primary microglia and astrocytes. Moreover, sulfatide rapidly triggered the phosphorylation of p38, ERK, and JNK within 30 min, and it markedly enhanced the NF binding activity to NF-kappa B and AP-1 binding elements. However, nonsulfated galactocerebroside, another major lipid component of myelin, had no effect on activation of glia. We further reveal that CD1d did not contribute to sulfatide-stimulated activation of MAPKs, although its expression was enhanced by sulfatide and sulfatide-treated microglial cells actually stimulated type II NKT cells. Sulfatide significantly stimulated the phosphorylation of MAPKs in glia from CD1d-deficient mice, and the phosphorylation levels were similar to those in wild-type littermates. Sulfatide-triggered inflammatory events appear to occur at least in part through an L-selectin-dependent mechanism. L-selectin was dramatically down-regulated upon exposure to sulfatide, and inhibition of L-selectin resulted in suppression of sulfatide-triggered responses. Collectively, these results show that abnormally released sulfatide at demyelinated regions may act as an endogenous stimulator in the brain immune system, thus causing and further exacerbating pathological conditions in the brain. The Journal of Immunology, 2008, 181: 8077-8087.