Centre for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée de la Chimie 3, B-4000 Liège, Belgium.
Chem Biol Interact. 2013 Jan 25;201(1-3):49-57. doi: 10.1016/j.cbi.2012.12.010. Epub 2013 Jan 2.
Phagocytic cells, especially neutrophils (PMNs) are specialized in the production of reactive oxygen species (ROS) to kill pathogenic agents, but an excessive ROS production is associated with tissue damages and inflammatory diseases. Phagocytes are thus prime therapeutic targets to control inflammatory events associated to ROS production. Nowadays, there is a growing interest for the use of polyphenols to modulate the inflammatory response. The aim of this work was to study the antioxidant effect of NDS27, a highly water-soluble form of the polyphenolic molecule curcumin, on in vitro stimulated equine PMNs and human promyelocytic leukemia cells (HL-60). NDS27 was either pre-incubated with cells and eliminated before their activation (intracellular effect) or let in the medium (extracellular effect). Our results indicate that NDS27 significantly and dose-dependently (10(-6) M-10(-4) M) inhibited the ROS production in both cell types without affecting their viability. NDS27 was able to cross and interact with cell membrane, especially for HL-60 cells, while we observed a better intracellular antioxidant effect with PMNs. The activity of myeloperoxidase (MPO) released by PMNs and HL-60 cells, was decreased by NDS27, but more efficiently for PMNs. These results suggested that the greater efficiency of NDS27 in PMNs is due to an inhibitory effect on cells which are more mature for ROS production, probably by targeting the enzymes implied in respiratory burst like MPO. The modulatory effect of NDS27 on the oxidant activity of cells involved in immune and inflammatory responses opens perspectives for a therapeutic control of pathologies with excessive inflammatory reactions.
吞噬细胞,尤其是中性粒细胞(PMN),专门产生活性氧物质(ROS)来杀死病原体,但过量的 ROS 产生与组织损伤和炎症性疾病有关。因此,吞噬细胞是控制与 ROS 产生相关的炎症事件的主要治疗靶点。如今,人们对使用多酚来调节炎症反应越来越感兴趣。这项工作的目的是研究 NDS27(多酚分子姜黄素的高度水溶性形式)对体外刺激的马中性粒细胞和人早幼粒细胞白血病细胞(HL-60)的抗氧化作用。NDS27 要么在细胞被激活之前与细胞预孵育并被清除(细胞内作用),要么让其留在培养基中(细胞外作用)。我们的结果表明,NDS27 显著且剂量依赖性地(10(-6) M-10(-4) M)抑制了两种细胞类型的 ROS 产生,而不影响其活力。NDS27 能够穿过并与细胞膜相互作用,尤其是对 HL-60 细胞,而我们观察到 PMN 细胞具有更好的细胞内抗氧化作用。NDS27 降低了 PMN 和 HL-60 细胞释放的髓过氧化物酶(MPO)的活性,但对 PMN 的效果更好。这些结果表明,NDS27 在 PMN 中更有效的原因可能是通过抑制产生 ROS 的细胞,特别是通过靶向 MPO 等与呼吸爆发相关的酶,来达到抑制作用。NDS27 对参与免疫和炎症反应的细胞氧化活性的调节作用为治疗过度炎症反应的病理提供了新的思路。