Department of Biomedical Sciences, University of Nevada Las Vegas School of Dental Medicine, 1001 Shadow Lane, Las Vegas, Nevada 89106, USA.
Inflamm Res. 2011 Aug;60(8):735-44. doi: 10.1007/s00011-011-0326-5. Epub 2011 Mar 24.
This study was designed to investigate and characterize the ability of platelet-activating factor (PAF) to induce the expression of platelet-activating factor acetylhydrolase (PAF-AH).
Ribonuclease protection assays and quantitative real-time PCR were used to investigate the ability of lipopolysaccharide (LPS) and PAF to regulate PAF-AH mRNA expression in human monocyte-macrophage 6 (MM6) cells. Pharmacological inhibitors of mitogen activated protein kinases (MAPK) and PAF receptor antagonists were used to investigate the mechanism of regulation of PAF-AH.
PAF-AH mRNA levels were increased upon exposure to LPS or PAF in a dose-dependent manner. LPS elicited a more potent and rapid increase in PAF-AH expression than the PAF-stimulated response. However, when administered concomitantly, PAF augmented the LPS-stimulated response. LPS-stimulated PAF-AH expression was susceptible to partial inhibition by a p38 MAPK inhibitor and PAF receptor antagonists. PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent.
The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways.
本研究旨在探讨并阐明血小板激活因子（PAF）诱导血小板激活因子乙酰水解酶（PAF-AH）表达的能力。
采用核糖核酸酶保护分析和实时定量 PCR 技术，研究脂多糖（LPS）和 PAF 对人单核细胞-巨噬细胞 6（MM6）细胞中 PAF-AH mRNA 表达的调节作用。采用丝裂原活化蛋白激酶（MAPK）的药理学抑制剂和 PAF 受体拮抗剂，研究 PAF-AH 调节的作用机制。
LPS 或 PAF 以剂量依赖的方式增加 PAF-AH mRNA 水平。LPS 诱导的 PAF-AH 表达增加比 PAF 刺激的反应更有效和更快。然而，当同时给药时，PAF 增强了 LPS 刺激的反应。LPS 刺激的 PAF-AH 表达易受 p38 MAPK 抑制剂和 PAF 受体拮抗剂的部分抑制。PAF 诱导的 PAF-AH 水平上调仅通过 PAF 受体介导，与 p38 MAPK 无关。
促炎介质 LPS 和 PAF 通过不同的信号通路增加 PAF-AH mRNA 水平。
Zotero 插件