Resveratrol modulates phagocytosis of bacteria through an NF-κB-dependent gene program
Resveratrol modulates phagocytosis of bacteria through an NF-κB-dependent gene program
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DOI：
10.1128/aac.00210-07
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发表时间：
2008-01-01
影响因子：
4.9
通讯作者：
Shibata, Ken-ichiro
中科院分区：
文献类型：
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作者：
Iyori, Mitsuhiro;Kataoka, Hideo;Shibata, Ken-ichiro
许多研究表明，白藜芦醇是一种植物防御素多酚化合物，其药理作用包括抗癌、抗炎以及增强抗应激能力。在这项研究中，我们检测了白藜芦醇是否影响巨噬细胞对细菌的吞噬以及在有或没有Toll样受体2(TLR2)的配体FSL-1的刺激下对转录因子NF-kappa B的激活。白藜芦醇以剂量依赖的方式抑制THP-1细胞和RAW264.7细胞对大肠杆菌和金黄色葡萄球菌的吞噬作用，而与FSL-1刺激无关。经FSL-1刺激后，稳定表达TLR2的HEK293细胞的核因子-kappaB活性也被白藜芦醇抑制。白藜芦醇还抑制核因子-kappaB的p65转位到细胞核内，并抑制THP-1细胞或RAW264.7细胞产生肿瘤坏死因子α。最近报道，TLR介导的信号通路导致吞噬细胞受体的mRNAs上调，包括清道夫受体和C型凝集素受体。本研究还表明，FSL-1诱导巨噬细胞清道夫受体-1、CD36、DC-SIGN和Dectin-1等吞噬细胞受体的mRNAs表达上调，白藜芦醇可抑制FSL-1诱导的mRNAs表达上调。此外，白藜芦醇还能抑制稳定表达DC-SIGN的HEK293细胞中DC-SIGN的表达，并显著抑制其吞噬功能。因此，本研究提示白藜芦醇通过下调吞噬细胞受体的表达和核因子-kappaB的活性来抑制巨噬细胞对细菌的吞噬作用。
Many studies have shown that the pharmacological effects of resveratrol, a phytoalexin polyphenolic compound, include protective effects against cancer and inflammation as well as enhancement of stress resistance. In this study, we examined whether resveratrol affected the phagocytosis of bacteria by macrophages and the activation of the transcription factor NF-kappa B after stimulation with or without the ligand FSL-1 for Toll-like receptor 2 (TLR2). Phagocytosis of Escherichia coli and of Staphylococcus aureus by THP-1 cells and RAW264.7 cells was inhibited by resveratrol in a dose-dependent manner regardless of stimulation with FSL-1. The NF-kappa B activity in HEK293 cells stably expressing TLR2 was also inhibited by resveratrol after stimulation with FSL-1. Resveratrol also inhibited both the translocation of p65 of NF-kappa B into nuclei in the transfectant and tumor necrosis factor alpha production by THP-1 cells or RAW264.7 cells. It has recently been reported that TLR-mediated signaling pathways lead to the upregulation of mRNAs of phagocytic receptors, including scavenger receptors and C-type lectin receptors. This study also demonstrated that FSL-1 induced the upregulation of mRNAs of phagocytic receptors such as macrophage scavenger receptor-1, CD36, DC-SIGN, and Dectin-1 and that the FSL-1-induced upregulation of their mRNAs was inhibited by resveratrol. In addition, it was found that the expression of DC-SIGN in HEK293 cells stably expressing DC-SIGN was reduced by resveratrol and that the phagocytic activity was significantly inhibited by resveratrol. Thus, this study suggests that resveratrol inhibited bacterial phagocytosis by macrophages by downregulating the expression of phagocytic receptors and NF-kappa B activity.