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首页> 外文期刊>Life sciences >Glucocorticoid receptor agonist compound K regulates Dectin-1-dependent inflammatory signaling through inhibition of reactive oxygen species.
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Glucocorticoid receptor agonist compound K regulates Dectin-1-dependent inflammatory signaling through inhibition of reactive oxygen species.

机译：糖皮质激素受体激动剂化合物K通过抑制活性氧来调节Dectin-1依赖性炎症信号。

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AIMS: Compound K (C-K; 20-O-D-glucopyranosyl-20(S)-protopanaxadiol) is a functional ligand of the glucocorticoid receptor (GR) and regulates toll-like receptor-4-dependent inflammation. Here, the role of C-K in the regulation of zymosan-mediated inflammation was investigated in murine bone marrow-derived macrophages and the murine macrophage cell line RAW264.7. MAIN METHODS: The in vitro regulatory effects of C-K on zymosan-induced cytokine production were measured by enzyme-linked immunosorbent assay. Phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, and p47phox was determined by detection of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase cytosolic subunit by Western blotting. The generation of reactive oxygen species (ROS) was assayed using specific immunofluorescent dyes. NADPH oxidase activities were measured by luminometric analysis. The histopathology of mouse livers and spleens was evaluated immunohistochemically. Dexamethasone, a well-known GR agonist, was used to study the effects of C-K. KEY FINDINGS: Pre-treatment with C-K significantly inhibited zymosan-mediated secretion of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-12 p40, and the activation of ERK1/2 and p38. C-K also markedly suppressed zymosan-mediated superoxide generation, NADPH oxidase activities, and Ser345-p47phox phosphorylation in macrophages. Blockade of Dectin-1 profoundly attenuated the inhibitory effects of C-K in zymosan-induced inflammation and ROS generation by macrophages. The in vivo administration of C-K significantly rescued cells from zymosan-induced lethal shock through inhibition of systemic inflammatory cytokine production. SIGNIFICANCE: The ability of C-K to regulate zymosan-induced inflammation through Dectin-1 suggests a novel approach for the control of excessive lethal inflammation.
机译：目的：化合物K（C-K; 20-O-D-吡喃葡萄糖基20（S）-原托那沙糖醇）是糖皮质激素受体（GR）的功能性配体，并调节toll样受体4依赖性炎症。在这里，在鼠骨髓来源的巨噬细胞和鼠巨噬细胞系RAW264.7中研究了C-K在酵母聚糖介导的炎症调节中的作用。主要方法：通过酶联免疫吸附法测定C-K对酵母聚糖诱导的细胞因子产生的体外调控作用。通过Western印迹检测烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶胞质亚基，确定细胞外信号调节激酶（ERK）1/2，p38和p47phox的磷酸化。使用特定的免疫荧光染料分析了活性氧（ROS）的产生。 NADPH氧化酶活性通过发光分析法测量。免疫组化评价了小鼠肝脏和脾脏的组织病理学。地塞米松是一种著名的GR激动剂，用于研究C-K的作用。主要发现：C-K预处理可显着抑制酵母聚糖介导的肿瘤坏死因子-α，白介素（IL）-6和IL-12 p40的分泌以及ERK1 / 2和p38的激活。 C-K还显着抑制巨噬细胞中的酵母聚糖介导的超氧化物生成，NADPH氧化酶活性和Ser345-p47phox磷酸化。 Dectin-1的封锁极大地减弱了C-K对酵母聚糖诱导的炎症和巨噬细胞产生ROS的抑制作用。通过抑制全身性炎性细胞因子的产生，体内施用C-K可将细胞从酵母聚糖诱导的致死性休克中大量拯救出来。意义：C-K通过Dectin-1调节酵母聚糖诱导的炎症的能力提出了一种控制过度致命性炎症的新方法。

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