Abstract
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.
Highlights
Interleukin 1 beta (IL-1β) is the most potent pro-inflammatory cytokine that is crucial in host-defense responses to infection and injury [1]
We demonstrated that flavonolignans, especially silybin and silychristin, are able to adenosine diphosphate (ADP)-induce blood platelets’ activation through interactions with the P2Y12 receptor [18]
Based on flow cytometry measurements, our results clearly indicate that IL-1β is statistically significant (p < 0.001) in the induction of the formation of platelets-leukocytes aggregates (Figure 1)
Summary
Interleukin 1 beta (IL-1β) is the most potent pro-inflammatory cytokine that is crucial in host-defense responses to infection and injury [1]. IL-1β is expressed by many cells and has multiple functions, including in local inflammation. IL-1β is produced by activated macrophages, endothelial cells, B cells, and fibroblasts. This potent pro-inflammatory cytokine was initially discovered and classified as the major endogenous pyrogen. IL-1β mediates the expression of a vast array of genes involved in secondary inflammation, which coordinate all aspects of local inflammation and attract and activate the cells of the adaptive immune system at the infection sites [2]. IL-1β is responsible for a broad spectrum of immune and inflammatory responses, induces T-cell and B-cell activation, and the synthesis of other pro-inflammatory cytokines
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