Differential anti-inflammatory pathway by xanthohumol in IFN-γ and LPS-activated macrophages
Differential anti-inflammatory pathway by xanthohumol in IFN-γ and LPS-activated macrophages
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DOI：
10.1016/j.intimp.2007.12.017
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发表时间：
2008-04-01
影响因子：
5.6
通讯作者：
Kang, Bok Yun
中科院分区：
文献类型：
--
作者：
Cho, Young-Chang;Kim, Hyun Jung;Kang, Bok Yun
巨噬细胞是负责先天免疫的主要细胞，它们被来自革兰氏阴性菌的LPS或来自宿主免疫细胞的IFN-γ激活对于控制感染是重要的。然而，巨噬细胞的压倒性激活可导致严重的炎症状态。本研究探讨了黄腐菌（XN）对激活的RAW264.7巨噬细胞中炎症效应因子（IL-1 β、TNF-α和iNOS）的抑制机制。XN是啤酒花中发现的主要异戊二烯化查耳酮，用于为啤酒添加苦味和风味。XN降低LPS受体组分如TLR 4和MD 2的表达，导致LPS激活的RAW 264. 7细胞中NF-κ B活化的抑制。在IFN-γ刺激的RAW264.7细胞中，STAT-1 α和IRF-1的结合活性被XN抑制。这表明XN使用不同的信号传导途径来抑制依赖于巨噬细胞中的刺激的过量炎症介质。(c))2008 Elsevier B. V.保留所有权利。
Macrophages are the main cells responsible for the innate immunity, and their activation by tipopolysaccharide (LPS) from Gram-negative bacteria or interferon (IFN)-gamma from host immune cells is important for controlling infections. However, the overwhelming activation of macrophages can cause a severe inflammatory state. This study investigated the inhibitory mechanism of xanthohumot (XN) against the inflammatory effectors (IL-1 beta, TNF-alpha, and iNOS) in activated RAW264.7 macrophages by using different stimuli such as LPS, IFN-gamma, or LPS plus IFN-gamma. XN is a major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. XN reduced the expression of the LPS receptor components such as TLR4 and MD2 resulting in the suppression of NF-kappa B activation in LPS-activated RAW264.7 cells. In the IFN-gamma stimulated RAW264.7 cells, the binding activity of STAT-1 alpha and IRF-1 was inhibited by XN. This suggests that differential signaling pathways are used by XN for the inhibition of excess inflammatory mediators depending on the stimuli in macrophages. (c)) 2008 Elsevier B.V. All rights reserved.