Squalene targets pro- and anti-inflammatory mediators and pathways to modulate over-activation of neutrophils, monocytes and macrophages
Squalene targets pro- and anti-inflammatory mediators and pathways to modulate over-activation of neutrophils, monocytes and macrophages
复制标题
DOI：
10.1016/j.jff.2015.03.009
复制
发表时间：
2015-04-01
影响因子：
5.6
通讯作者：
Alarcon-de-la-Lastra, Catalina
中科院分区：
文献类型：
--
作者：
Cardeno, Ana;Aparicio-Soto, Marina;Alarcon-de-la-Lastra, Catalina
角鲨烯是一种天然的三萜，是人类饮食中不可或缺的一部分。越来越多的证据表明，角鲨烯具有抗氧化、保护心脏和抗癌活性。然而，其抗炎特性尚不清楚。研究了角鲨烯对脂多糖（LPS）介导的小鼠巨噬细胞和人单核细胞及中性粒细胞炎症反应的影响。角鲨烯降低细胞内ROS、亚硝酸盐、细胞因子（tnf - α、IL-1 β、IL-6和ifn - γ）和促炎酶（iNOS、COX-2和MPO）的水平，包括降低TLR4和nf - κ B （I κ B α）、MAPKs （JNK）和MMPs（1,3和9）介导的信号通路关键蛋白的表达。此外，角鲨烯可提高抗炎酶（HO-1）和转录因子（Nrf2和PPAR γ）的表达水平。本研究证实，角鲨烯在以中性粒细胞/单核细胞/巨噬细胞过度激活为特征的炎症条件下具有显著的治疗潜力，从而有效地终止炎症反应。(C) 2015 Elsevier Ltd.版权所有。
Squalene is a natural triterpene consumed as an integral part of the human diet. Increasing evidence demonstrates that squalene has antioxidant, cardioprotective and anti-carcinogenic activities. Nevertheless, its anti-inflammatory properties remain unclear. The effects of squalene on lipopolysaccharide (LPS)-mediated inflammatory response in murine macrophages and human monocytes and neutrophils were investigated. Squalene reduced intracellular levels of ROS, nitrites, cytokines (TNF-alpha, IL-1 beta, IL-6 and IFN-gamma) and pro-inflammatory enzymes (iNOS, COX-2 and MPO), including a decreased expression of TLR4 and key proteins for signalling pathways mediated by NF-kappa B (I kappa B alpha), MAPKs (JNK) and MMPs (1, 3 and 9). In addition, squalene enhanced expression levels of anti-inflammatory enzymes (HO-1) and transcription factors (Nrf2 and PPAR gamma). This study establishes that squalene has significant potential for management of inflammatory conditions characterized by an over-activation of neutrophils/monocytes/macrophages and thereby for the efficient termination of the inflammatory response. (C) 2015 Elsevier Ltd. All rights reserved.