Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuán 4, 41009, Sevilla, Spain.
Eur J Nutr. 2014 Dec;53(8):1707-17. doi: 10.1007/s00394-014-0677-0. Epub 2014 Apr 11.
Regulation of liver X receptors (LXRs) is essential for cholesterol homeostasis and inflammation. The present study was conducted to determine whether oleic acid (OA) could regulate mRNA expression of LXRα and LXRα-regulated genes and to assess the potential promotion of oxidative stress by OA in neutrophils.
Human neutrophils were treated with OA at different doses and LXR target gene expression, oxidative stress production, lipid efflux and inflammation state were analyzed.
We describe that mRNA synthesis of both LXRα and ABCA1 (a reverse cholesterol transporter) was induced by OA in human neutrophils. This fatty acid enhanced the effects of LXR ligands on ABCA1 and LXR expression, but it decreased the mRNA levels of sterol regulatory element-binding protein 1c (a transcription factor that regulates the synthesis of triglycerides). Although OA elicited a slight oxidative stress in the short term (15-30 min) in neutrophils, it is unlikely that this is relevant for the modulation of transcription in our experimental conditions, which involve longer incubation time (i.e., 6 h). Of physiological importance is our finding that OA depresses intracellular lipid levels and that markers of inflammation, such as ERK1/2 and p38 mitogen-activated protein kinase phosphorylation, were decreased by OA treatment. In addition, 200 μM OA reduced the migration of human neutrophils, another marker of the inflammatory state. However, OA did not affect lipid peroxidation induced by pro-oxidant agents.
This work presents for the first time evidence that human neutrophils are highly sensitive to OA and provides novel data in support of a protective role of this monounsaturated acid against the activation of neutrophils during inflammation.
肝脏 X 受体（LXRs）的调节对于胆固醇稳态和炎症至关重要。本研究旨在确定油酸（OA）是否可以调节 LXRα 和 LXRα 调节基因的 mRNA 表达，并评估 OA 在中性粒细胞中促进氧化应激的潜力。
用不同剂量的 OA 处理人中性粒细胞，分析 LXR 靶基因表达、氧化应激产物、脂质外排和炎症状态。
我们描述了 OA 在人中性粒细胞中诱导 LXRα 和 ABCA1（一种逆胆固醇转运体）的 mRNA 合成。这种脂肪酸增强了 LXR 配体对 ABCA1 和 LXR 表达的作用，但降低了固醇调节元件结合蛋白 1c（一种调节甘油三酯合成的转录因子）的 mRNA 水平。尽管 OA 在短时间内（15-30 分钟）在中性粒细胞中引起轻微的氧化应激，但在我们的实验条件下，这不太可能与转录的调节有关，因为我们的实验条件涉及更长的孵育时间（即 6 小时）。具有生理意义的是，我们发现 OA 降低了细胞内脂质水平，OA 处理还降低了 ERK1/2 和 p38 丝裂原活化蛋白激酶磷酸化等炎症标志物的水平。此外，200μM OA 减少了人中性粒细胞的迁移，这是炎症状态的另一个标志物。然而，OA 并不影响由促氧化剂诱导的脂质过氧化。
这项工作首次证明人中性粒细胞对 OA 高度敏感，并提供了新的数据支持这种单不饱和酸在炎症期间对中性粒细胞激活具有保护作用。
