CD38 is required for priming by TNF-alpha: a mechanism for extracellular coordination of cell fate.
CD38 is required for priming by TNF-alpha: a mechanism for extracellular coordination of cell fate.
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CD38 是 TNF-α 启动所必需的：TNF-α 是细胞命运的细胞外协调机制。
DOI：
10.1152/ajprenal.00381.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Zaidi,Mone
中科院分区：
文献类型：
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作者：
Iqbal,Jameel;Zaidi,Mone
细胞因子是调节其靶细胞分化或活化的蛋白质信使。骨髓巨噬细胞可以变成活化的组织巨噬细胞、树突状细胞或破骨细胞，这取决于它们暴露于哪种细胞因子。然而，一种细胞因子通常可以诱导不同的结果，这表明需要其他信号来建立结果的特异性。我们假设这些信号可能来自于局部环境，并有助于启动细胞对特定结果做出反应。本文显示，细胞因子TNF-α能够通过上调NAD酶CD 38影响巨噬细胞的命运。CD 38上调引发巨噬细胞，使得由炎性刺激诱导的信号增强，而导致破骨细胞形成的信号被抑制。我们发现TNF-α诱导的CD 38表达对破骨细胞标志物的表达有负面影响，同时它通过降低ERK 1/2磷酸化和增加NF-κB活化来增强炎症基因的表达。此外，它表明，CD 38可以减少破骨细胞和增加炎症基因的诱导，通过降低细胞组蛋白脱乙酰酶活性。这些结果证明了细胞因子如何引发细胞向特定谱系分化或获得增强的活化特征。由于CD 38是一种胞外酶，我们认为细胞外NAD+代谢的调节可能是协调局部环境中细胞命运的独特机制。
Cytokines are protein messengers that act to modulate the differentiation or activation of their target cells. Bone marrow macrophages can become activated tissue macrophages, dendritic cells, or osteoclasts depending on to which cytokines they are exposed. However, one cytokine can often induce divergent outcomes, suggesting that other signals are needed to establish the specificity of the result. We hypothesize that these signals may derive from the local environment and serve to prime cells to respond toward a specific outcome. Here, it is shown that the cytokine TNF-α is capable of affecting the fate of macrophages by upregulating the NADase CD38. CD38 upregulation primes macrophages, such that signals induced by inflammatory stimuli are augmented, while those leading to osteoclast formation are inhibited. We show that TNF-α-induced CD38 expression negatively affects the expression of osteoclast markers, while it enhances inflammatory gene expression by decreasing ERK1/2 phosphorylation and increasing NF-κB activation. Furthermore, it is shown that CD38 may reduce osteoclastogenesis and increase inflammatory gene induction by decreasing cellular histone deacetylase activity. These results provide a demonstration of how a cytokine can prime cells to differentiate toward a certain lineage or acquire enhanced activation characteristics. Since CD38 is an ectoenzyme, we suggest that the modulation of extracellular NAD+metabolism likely serves as a unique mechanism to coordinate the fate of cells within a local environment.