Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages
Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages
复制标题
DOI：
10.1016/j.molimm.2013.05.005
复制
发表时间：
2013-12-01
影响因子：
3.6
通讯作者：
Benko, Szilvia
中科院分区：
文献类型：
--
作者：
Budai, Marietta M.;Varga, Aliz;Benko, Szilvia
芦荟在传统中草药中被用作免疫调节剂，具有抗炎作用。然而，其在IL-1β炎性细胞因子产生中的作用尚未被研究。IL-1β的产生通过Nlrp3炎症体的活性在转录和翻译后水平受到严格调控。本研究旨在探讨芦荟对内毒素激活的人THP-1细胞和单核细胞来源的巨噬细胞产生IL-1β的分子机制的影响。结果表明，芦荟显著降低IL-8、TNF-α、IL-6和IL-1β细胞因子的产生，并呈剂量依赖关系。这种抑制作用在原代细胞中要明显得多。我们发现芦荟可抑制脂多糖诱导的巨噬细胞原IL-1β、Nirp3、caspase-1的表达以及P2X7受体的表达。此外，库拉索芦荟可抑制脂多糖诱导的细胞内核因子-kappa B、p38、JNK和ERK等信号通路的激活。总之，我们首次证明芦荟维拉索介导的IL-1β的强烈减少可能是通过抑制特定的信号转导途径而导致前IL-1β和Nirp3炎症体成分表达减少的结果。此外，我们还发现，ATP感受器P2X7受体的表达也被芦荟下调，这也可能是导致IL-1β细胞因子分泌减弱的原因之一。这些结果可能为调节炎症小体介导的反应提供一种新的治疗方法。(C)2013爱思唯尔有限公司。保留所有权利。
Aloe vera has been used in traditional herbal medicine as an immunomodulatory agent inducing anti-inflammatory effects. However, its role on the IL-1 beta inflammatory cytokine production has not been studied. IL-1 beta production is strictly regulated both at transcriptional and posttranslational levels through the activity of Nlrp3 inflammasome. In this study we aimed to determine the effect of Aloe vera on the molecular mechanisms of NIrp3 inflammasome-mediated IL-1 beta production in LPS-activated human THP-1 cells and monocyte-derived macrophages. Our results show that Aloe vera significantly reduced IL-8, TNF alpha, IL-6 and IL-1 beta cytokine production in a dose dependent manner. The inhibitory effect was substantially more pronounced in the primary cells. We found that Aloe vera inhibited the expression of pro-IL-1 p, Nirp3, caspase-1 as well as that of the P2X7 receptor in the LPS-induced primary macrophages. Furthermore, LPS-induced activation of signaling pathways like NF-kappa B, p38, JNK and ERK were inhibited by Aloe vera in these cells.Altogether, we show for the first time that Aloe vera-mediated strong reduction of IL-1 beta appears to be the consequence of the reduced expression of both pro-IL-1 beta as well as Nirp3 inflammasome components via suppressing specific signal transduction pathways. Furthermore, we show that the expression of the ATP sensor P2X7 receptor is also downregulated by Aloe vera that could also contribute to the attenuated IL-1 beta cytokine secretion. These results may provide a new therapeutic approach to regulate inflammasome-mediated responses. (C) 2013 Elsevier Ltd. All rights reserved.