Cho Young-Chang, Kim Hyun Jung, Kim Young-Jun, Lee Kwang Youl, Choi Hyun Jin, Lee Ik-Soo, Kang Bok Yun
College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Int Immunopharmacol. 2008 Apr;8(4):567-73. doi: 10.1016/j.intimp.2007.12.017. Epub 2008 Jan 24.
Macrophages are the main cells responsible for the innate immunity, and their activation by lipopolysaccharide (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 xanthohumol (XN) against the inflammatory effectors (IL-1beta, 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-kappaB activation in LPS-activated RAW264.7 cells. In the IFN-gamma stimulated RAW264.7 cells, the binding activity of STAT-1alpha 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.
巨噬细胞是负责固有免疫的主要细胞，革兰氏阴性菌的脂多糖（LPS）或宿主免疫细胞的干扰素（IFN）-γ对其激活对于控制感染很重要。然而，巨噬细胞的过度激活会导致严重的炎症状态。本研究通过使用不同刺激物如LPS、IFN-γ或LPS加IFN-γ，研究了黄腐酚（XN）对活化的RAW264.7巨噬细胞中炎症效应因子（IL-1β、TNF-α和诱导型一氧化氮合酶）的抑制机制。XN是啤酒花中发现的一种主要的异戊烯基化查耳酮，用于为啤酒增添苦味和风味。XN降低了LPS受体成分如TLR4和MD2的表达，导致LPS激活的RAW264.7细胞中NF-κB激活受到抑制。在IFN-γ刺激的RAW264.7细胞中，XN抑制了STAT-1α和IRF-1的结合活性。这表明XN根据巨噬细胞中的刺激物使用不同的信号通路来抑制过量的炎症介质。
