Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Department of Cardiology with Emphasis on Electrophysiology, University Heart Centre, University Hospital Hamburg-Eppendorf, 20251 Hamburg, Germany.
Dis Markers. 2021 Mar 18;2021:6622701. doi: 10.1155/2021/6622701. eCollection 2021.
In several preclinical and models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an model of acute inflammation.
HepG2 cells were stimulated with IL-1 and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF- release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed.
In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1-induced IL-6 and TNF- release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1 stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1-induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation.
EtOH exerts anti-inflammatory potential in this model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.
在几种急性炎症的临床前和临床模型中，酒精（乙醇，EtOH）被描述为一种免疫调节剂。同样，在不同的病理情况下，临床观察也证实了 EtOH 具有促炎或抗炎作用。肝脏在免疫和酒精代谢中起着重要作用；因此，我们分析了 EtOH 在急性炎症模型中对人肝细胞炎症反应的剂量和时间依赖性影响。
用 IL-1 刺激 HepG2 细胞，然后用低剂量（85mM，LoD）或高剂量（170mM，HiD） EtOH 急性暴露 1 小时或长期暴露 72 小时。通过 ELISA 测定 IL-6 和 TNF-的释放。分析细胞活力、分离的中性粒细胞与 HepG2 单层的黏附、ICAM-1 的表达以及应激诱导的蛋白激酶/c-Jun N 末端激酶（SAPK/JNK）或信号转导和转录激活因子 3（STAT3）的激活。
在本实验设计中，EtOH 对细胞活力没有显著影响。急性和长期暴露于 EtOH 可显著降低剂量非依赖性 IL-1 诱导的 IL-6 和 TNF-释放，以及与预处理 HepG2 细胞的黏附能力。急性 EtOH 暴露显著降低了表达 ICAM-1 的细胞百分比。IL-1 刺激显著增加了 SAPK/JNK 的激活。然而，低剂量 EtOH 暴露显著降低了这种激活，与高剂量 EtOH 暴露相反。急性暴露于低剂量 EtOH 显著降低了 IL-1 诱导的 STAT3 激活，而急性暴露于高剂量 EtOH 或长期暴露于 EtOH 对 STAT3 激活没有影响。
在这种肝炎症模型中，EtOH 表现出抗炎潜力。这些作用与 EtOH 降低 JNK/STAT3 的激活有关，特别是在急性暴露于低剂量 EtOH 的情况下。
