TNF-alpha increases ceramide without inducing apoptosis in alveolar type II epithelial cells.
TNF-alpha increases ceramide without inducing apoptosis in alveolar type II epithelial cells.
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TNF-α 增加神经酰胺而不诱导肺泡 II 型上皮细胞凋亡。
DOI：
10.1152/ajplung.1999.276.3.l481
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Koretzky,GA
中科院分区：
文献类型：
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作者：
Mallampalli,RK;Peterson,EJ;Carter,AB;Salome,RG;Mathur,SN;Koretzky,GA
神经酰胺是一种生物活性脂质介质，已观察到其在体外诱导细胞凋亡。本研究旨在确定体内给予肿瘤坏死因子-α（TNF-α）后产生的内源性神经酰胺是否增加原代大鼠肺泡II型上皮细胞的凋亡。肠内滴注TNF-α（5 μg）可导致鞘磷脂减少和中性鞘磷脂酶激活。这些变化与肺神经酰胺含量的显著增加有关。TNF-α同时激活p42/44细胞外信号相关激酶，并诱导肺中核因子-κB活化。亚二倍体细胞核研究表明，与对照细胞相比，分离后的细胞内TNF-α并不增加II型细胞凋亡。一个新的观察，从单独的体外研究表明，II型细胞经历一段时间后，在培养中的细胞凋亡逐渐增加，这是一个过程，加速细胞暴露于紫外线。然而，与细胞可渗透的神经酰胺TNF-α或相关配体抗CD 95一起培养的细胞并没有使细胞凋亡增加到高于对照水平。结果表明，TNF-α激活鞘磷脂水解产生的神经酰胺可能激活丝裂原活化蛋白激酶和核因子-κB途径，而不增加II型细胞的程序性细胞死亡。
Ceramide is a bioactive lipid mediator that has been observed to induce apoptosis in vitro. The purpose of this study was to determine whether endogenous ceramide, generated in response to in vivo administration of tumor necrosis factor-α (TNF-α), increases apoptosis in primary rat alveolar type II epithelial cells. Intratracheal instillation of TNF-α (5 μg) produced a decrease in sphingomyelin and activation of a neutral sphingomyelinase. These changes were associated with a significant increase in lung ceramide content. TNF-α concomitantly activated the p42/44 extracellular signal-related kinases and induced nuclear factor-κB activation in the lung. Hypodiploid nuclei studies revealed that intratracheal TNF-α did not increase type II cell apoptosis compared with that in control cells after isolation. A novel observation from separate in vitro studies demonstrated that type II cells undergo a gradual increase in apoptosis after time in culture, a process that was accelerated by exposure of cells to ultraviolet light. However, culture of cells with a cell-permeable ceramide, TNF-α, or a related ligand, anti-CD95, did not increase apoptosis above the control level. The results suggest that ceramide resulting from TNF-α activation of sphingomyelin hydrolysis might activate the mitogen-activated protein kinase and nuclear factor-κB pathways without increasing programmed cell death in type II cells.