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硒代蛋氨酸通过靶向 NF-κB 信号通路介导 LPS 诱导的 U937 细胞抗炎作用。

SeMet mediates anti-inflammation in LPS-induced U937 cells targeting NF-κB signaling pathway.

机构信息

Department of Orthopedic Surgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China,

出版信息

Inflammation. 2015 Apr;38(2):736-44. doi: 10.1007/s10753-014-9984-0.

DOI:10.1007/s10753-014-9984-0
PMID:25145772
Abstract

In previous studies, selenium (Se) was reported to play critical roles in anti-inflammatory activities. Nevertheless, limited information could be obtained during inflammation about selenomethionine (SeMet) in U937 human macrophage cells. The purpose of this study was to investigate the effects of SeMet on the inflammatory responses to lipopolysaccharide (LPS)-induced U937 macrophage cells and the signaling pathways targeted. U937 cells were pretreated with SeMet (1 μM) and subsequently induced with LPS (1 μg/ml) for 24 h. In the cell counting kit-8 assay (CCK-8), SeMet significantly inhibits the proliferation of U937 cells. SeMet also inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) stimulated by LPS. In the Western blot assay and real-time polymerase chain reaction (RT-PCR), SeMet significantly reduced protein expression and production of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and COX-2 in U937 cells. Furthermore, SeMet markedly suppressed the LPS-mediated activation of nuclear factor-kappa B (NF-κB) by blocking the degradation of inhibitor-κB proteins (IκBα) and lessening the translocations of P50 subunit content of NF-κB in the nucleus. These findings suggested the anti-inflammatory activity of SeMet in U937 cells; indicating that SeMet might be a potential treatment for inflammation therapy.

摘要

在之前的研究中,硒(Se)被报道在抗炎活性中发挥关键作用。然而,在炎症期间,关于 U937 人巨噬细胞中的硒代蛋氨酸(SeMet)的信息有限。本研究旨在探讨 SeMet 对脂多糖(LPS)诱导的 U937 巨噬细胞炎症反应及靶向信号通路的影响。用 SeMet(1 μM)预处理 U937 细胞,随后用 LPS(1 μg/ml)诱导 24 h。在细胞计数试剂盒-8 测定(CCK-8)中,SeMet 显著抑制 U937 细胞的增殖。SeMet 还抑制 LPS 刺激的一氧化氮(NO)和前列腺素 E2(PGE2)的产生。在 Western blot 测定和实时聚合酶链反应(RT-PCR)中,SeMet 显著降低了 U937 细胞中诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)和 COX-2 的蛋白表达和产生。此外,SeMet 通过阻断抑制剂-κB 蛋白(IκBα)的降解和减少 NF-κB 核内 P50 亚基含量的转位,显著抑制了 LPS 介导的核因子-κB(NF-κB)的激活。这些发现表明 SeMet 在 U937 细胞中具有抗炎活性;表明 SeMet 可能是一种潜在的炎症治疗方法。

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