Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Laboratory Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Nutrients. 2017 Sep 15;9(9):1022. doi: 10.3390/nu9091022.
Interleukin-1 beta (IL-1β)-the most potent pro-inflammatory is responsible for a broad spectrum of immune and inflammatory responses, it induces T-cell and B-cell activation and consequently the synthesis of other pro-inflammatory cytokines (such as IFN-γ and TNF). IL-1β induces the formation of blood platelet-leukocyte aggregates (PLAs), which suggests that IL-1β significantly affects the cross-talk between blood platelets and the immune response system, leading to coronary thrombosis. The aim of our study is to investigate the effect of flavonolignans (silybin, silychristin and silydianin) on the IL-1β-induced interaction between platelets and leukocytes, as well as on the expression and the secretion of pro-inflammatory factors. Whole blood samples were pre-incubated with commercially available flavonolignans (silybin, silychristin and silydianin) in a concentration range of 10-100 µM (30 min, 37 °C). Next, samples were activated by IL-1β for 1 h. Blood platelet-leukocyte aggregates were detected by using the double-labeled flow cytometry (CD61/CD45). The level of produced cytokines was estimated via the ELISA immunoenzymatic method. IFN-γ and TNF gene expression was evaluated using Real Time PCR with TaqMan arrays. We observed that in a dose-dependent manner, silybin and silychristin inhibit the IL-1β-induced formation of blood platelet-leukocyte aggregates in whole blood samples, as well as the production of pro-inflammatory cytokines-IL-2, TNF, INF-α, and INF-γ. Additionally, these two flavonolignans abolished the IL-1β-induced expression of mRNA for IFN-γ and TNF. Our current results demonstrate that flavonolignans can be novel compounds used in the prevention of cardiovascular diseases with dual-use action as antiplatelet and anti-inflammatory agents.
白细胞介素-1β（IL-1β）是最有效的促炎因子，负责广泛的免疫和炎症反应，它诱导 T 细胞和 B 细胞的激活，从而导致其他促炎细胞因子（如 IFN-γ 和 TNF）的合成。IL-1β诱导血小板-白细胞聚集物（PLAs）的形成，这表明 IL-1β显著影响血小板与免疫系统之间的相互作用，导致冠状动脉血栓形成。我们的研究目的是研究黄酮木脂素（水飞蓟宾、水飞蓟素和水飞蓟宁）对 IL-1β诱导的血小板与白细胞相互作用的影响，以及对促炎因子的表达和分泌的影响。全血样本用市售的黄酮木脂素（水飞蓟宾、水飞蓟素和水飞蓟宁）在 10-100 µM 的浓度范围内孵育（30 分钟，37°C）。然后，用 IL-1β 激活样本 1 小时。用双标记流式细胞术（CD61/CD45）检测血小板-白细胞聚集物。通过 ELISA 免疫酶法估计产生的细胞因子的水平。用 TaqMan 阵列实时 PCR 评估 IFN-γ 和 TNF 基因表达。我们观察到，水飞蓟宾和水飞蓟素以剂量依赖的方式抑制全血样本中 IL-1β诱导的血小板-白细胞聚集物的形成，以及促炎细胞因子-IL-2、TNF、INF-α和 INF-γ的产生。此外，这两种黄酮木脂素消除了 IL-1β诱导的 IFN-γ 和 TNF mRNA 的表达。我们目前的结果表明，黄酮木脂素可以作为预防心血管疾病的新型化合物，具有双重作用，既可以作为抗血小板药物，也可以作为抗炎药物。
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