The bioactive sphingolipid ceramide 1-phosphate (C1P) regulates key physiologic cell functions and is implicated in a number of metabolic alterations and pathological processes. Initial studies using different types of fibroblasts and monocytes/macrophages revealed that C1P was mitogenic and that it promoted cell survival through inhibition of apoptosis. Subsequent studies implicated C1P in inflammatory responses with a specific role as pro-inflammatory agent. Specifically, C1P potently stimulated cytosolic phospholipase A2 (cPLA2) resulting in elevation of arachidonic acid and pro-inflammatory eicosanoid levels. However, increasing experimental evidence suggests that C1P can also exert anti-inflammatory actions in some cell types and tissues. Specifically, it has been demonstrated that C1P inhibits the release of pro-inflammatory cytokines and blocks activation of the pro-inflammatory transcription factor NF-κB in some cell types. Moreover, C1P was shown to increase the release of anti-inflammatory interleukin-10 in macrophages, and to overcome airway inflammation and reduce lung emphysema in vivo. Noteworthy, C1P stimulated cell migration, an action that is associated with diverse physiological cell functions, as well as with inflammatory responses and tumor dissemination. More recently, ceramide kinase (CerK), the enzyme that produces C1P in mammalian cells, has been shown to be upregulated during differentiation of pre-adipocytes into mature adipocytes, and that exogenous C1P, acting through a putative Gi protein-coupled receptor, negatively regulates adipogenesis. Although the latter actions seem to be contradictory, it is plausible that exogenous C1P may balance the adipogenic effects of intracellularly generated (CerK-derived) C1P in adipose tissue. The present review highlights novel signaling aspects of C1P and its impact in the regulation of cell growth and survival, inflammation and tumor dissemination.

中文翻译：

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神经酰胺1-磷酸的新型信号传导方面。

具有生物活性的鞘脂神经酰胺1-磷酸酯（C1P）调节关键的生理细胞功能，并参与许多代谢改变和病理过程。使用不同类型的成纤维细胞和单核细胞/巨噬细胞的初步研究表明，C1P具有促有丝分裂作用，并通过抑制细胞凋亡来促进细胞存活。随后的研究表明C1P参与了炎症反应，并具有特定的促炎作用。具体而言，C1P有效刺激胞质磷脂酶A2（cPLA2），导致花生四烯酸水平升高和促炎性类花生酸水平升高。但是，越来越多的实验证据表明，C1P还可以在某些细胞类型和组织中发挥抗炎作用。特别，已经证明，C1P在某些细胞类型中抑制促炎细胞因子的释放并阻断促炎转录因子NF-κB的活化。此外，C1P被证明可增加巨噬细胞中抗炎性白介素10的释放，并在体内克服气道炎症并减少肺气肿。值得注意的是，C1P刺激了细胞迁移，这一作用与多种生理细胞功能以及炎症反应和肿瘤扩散有关。最近，神经酰胺激酶（CerK）（一种在哺乳动物细胞中产生C1P的酶）已被证明在前脂肪细胞分化为成熟脂肪细胞的过程中被上调，而外源的C1P通过一个公认的Gi蛋白偶联受体发挥负作用。调节脂肪形成。尽管后者的作用似乎是矛盾的，但外源性C1P可能平衡脂肪组织中细胞内生成（CerK衍生）的C1P的成脂作用是合理的。本综述着重介绍了C1P的新型信号传导方面及其对调节细胞生长和存活，炎症和肿瘤扩散的影响。