The 2-series prostaglandins suppress VLDL secretion in an inflammatory condition-dependent manner in primary rat hepatocytes
The 2-series prostaglandins suppress VLDL secretion in an inflammatory condition-dependent manner in primary rat hepatocytes
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DOI：
10.1016/j.bbalip.2006.02.003
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发表时间：
2006-02-01
影响因子：
4.8
通讯作者：
Chico, Y
中科院分区：
文献类型：
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作者：
Pérez, S;Aspichueta, P;Chico, Y
在肝脏中，主要由活化的非实质细胞产生的前列腺素（PG）可以在稳态和炎症过程中调节实质细胞的功能。前列腺素是否在这两种情况下调节肝细胞 VLDL 组装/分泌表型仍未解决。我们试图确定 PGE(2)、PGD(2) 和 PGF(2α)（5 和 50 μM）是否以及如何在静息和白细胞介素 6 (IL-6) 刺激的大鼠肝细胞中的 VLDL 分泌调节中发挥作用。前列腺素导致静息培养 24 小时细胞的 VLDL apoB 和脂质分泌量出现类似的、浓度依赖性的减少。此外，每个 apoB 拷贝招募的每种脂质类别较少，与颗粒尺寸减小、脂肪生成和胆固醇生成以及细胞三酰甘油循环受损相关。随着短暂的 PGD(2) 和 PGF(2α) 促进的 apoB mRNA 减少，三酰甘油输出减少发生得很早。 IL-6 显着增加了缺乏三酰甘油的 VLDL 中 apoB mRNA 的表达及其蛋白的分泌。后者被 PGE(2) 独特地削弱，其不影响基础或 IL-6 激活的 apoB 基因表达。总的来说，我们的研究结果显示了 2 系列前列腺素在 VLDL 分泌调节中的基于炎症状况的作用。而在未受刺激的肝细胞中，它们都会抑制 VLDL-apoB 输出，干扰脂蛋白组装的脂质供应，并可能被视为前列腺癌，而抗炎 PGE(2) 会拮抗 IL-6 促进的 VLDL 分泌，有助于恢复肝脏稳态。 (c) 2006 Elsevier B.V. 保留所有权利。
In the liver, prostaglandins (PG) generated mainly by activated non-parenchymal cells can modulate the parenchymal cell function during homeostasis and inflammation. Whether prostaglandins regulate the hepatocyte VLDL assembling/secretor phenotype in both conditions remains unresolved. We sought to determine whether and how PGE(2), PGD(2), and PGF(2 alpha) (5 and 50 mu M) have a role in VLDL secretion regulation in resting and interleukin-6 (IL-6) stimulated rat hepatocytes. Prostaglandins led to comparable, concentration -dependent reductions in the secretion of VLDL apoB and lipids by resting, 24 h-cultured cells. Moreover, each apoB copy recruited less of each lipid class, correlating with reduced particle size, lipogenesis and cholesterogenesis, and impaired cellular triacylglycerol recycling. Triacylglycerol output reduction occurred early, as the transient PGD(2)- and PGF(2 alpha)-promoted apoB mRNA decreases. IL-6 markedly increased the apoB mRNA expression and the secretion of its protein in triacylglycerol-poor VLDL. The latter was uniquely blunted by PGE(2), which unaffected basal or IL-6-activated apoB gene expression. Collectively, Our findings show inflammation condition-based roles for 2-series-prostaglandins in VLDL secretion modulation. Whereas in non-stimulated hepatocytes, they all inhibited VLDL-apoB output, interfered with lipid provision for lipoprotein assembly and may be regarded as prosteatotic, the anti-inflammatory PGE(2) antagonized the IL-6-promoted VLDL secretion contributing in restoring liver homeostasis. (c) 2006 Elsevier B.V. All rights reserved.