γ-Tocotrienol inhibits lipopolysaccharide-induced interlukin-6 and granulocyte colony-stimulating factor by suppressing C/EBPβ and NF-κB in macrophages.
γ-Tocotrienol inhibits lipopolysaccharide-induced interlukin-6 and granulocyte colony-stimulating factor by suppressing C/EBPβ and NF-κB in macrophages.
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DOI：
10.1016/j.jnutbio.2012.08.015
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Jiang Q
中科院分区：
文献类型：
--
作者：
Wang Y;Jiang Q
由巨噬细胞产生的细胞因子有助于炎症相关疾病的发病机制。在此，我们发现天然维生素E形式γ-生育三烯酚（γ-TE）抑制脂多糖（LPS）诱导的小鼠RAW 267.4巨噬细胞中白细胞介素-6（IL-6）的产生，而不影响TNFα、IL-10或环氧合酶-2（考克斯-2）的上调。机制研究表明，核因子（NF）-κB，而不是JNK，p38或ERK MAP激酶，对IL-6的产生是重要的，γ-TE处理阻断NF-κB活化。相反，在RAW细胞中，考克斯-2似乎受p38 MAPK的调节，但γ-TE对LPS刺激的p38磷酸化没有影响。尽管IL-6是必需的，但TNFα或其他细胞因子对NF-κB的激活不足以诱导IL-6，LPS除外。CCAAT增强子结合蛋白β（C/EBPβ）似乎参与IL-6的形成，因为LPS诱导C/EBPβ上调，这与IL-6的产生平行，并且用siRNA敲低C/EBPβ导致IL-6减少。LPS而不是单个细胞因子能够刺激巨噬细胞中的C/EBPβ和IL-6。与其对IL-6的抑制作用一致，γ-TE减弱LPS诱导的C/EBPβ上调，而不影响C/EBPδ。γ-TE还可降低LPS刺激的粒细胞集落刺激因子（G-CSF）（一种C/EBPβ靶基因）。与RAW267.4细胞相比，γ-TE对LPS诱导的NF-κB、C/EPBβ和C/EBPδ的激活有相似或更强的抑制作用，对IL-6和G-CSF的抑制作用更强。本研究表明，γ-TE通过抑制巨噬细胞NF-κB和C/EBP的活化而发挥抗炎作用。
Cytokines generated from macrophages contributes to pathogenesis of inflammation-associated diseases. Here we show that gamma-tocotrienol (γ-TE), a natural vitamin E form, inhibits lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) production without affecting TNFα, IL-10 or cyclooxygenase-2 (COX-2) up-regulation in murine RAW267.4 macrophages. Mechanistic studies indicate that nuclear factor (NF)-κB, but not JNK, p38 or ERK MAP kinases, is important to IL-6 production and γ-TE treatment blocks NF-κB activation. In contrast, COX-2 appears to be regulated by p38 MAPK in RAW cells, but γ-TE has no effect on LPS-stimulated p38 phosphorylation. Despite necessary for IL-6, NF-κB activation by TNFα or other cytokines is not sufficient for IL-6 induction with exception of LPS. CCAAT-enhancer binding protein β (C/EBPβ) appears to be involved in IL-6 formation, because LPS induces C/EBPβ up-regulation, which parallels IL-6 production, and knockdown of C/EBPβ with siRNA results in diminished IL-6. LPS but not individual cytokines is capable of stimulating C/EBPβ and IL-6 in macrophages. Consistent with its dampening effect on IL-6, γ-TE blunts LPS-induced up-regulation of C/EBPβ without affecting C/EBPδ. γ-TE also decreases LPS-stimulated granulocyte-colony stimulating factor (G-CSF), a C/EBPβ target gene. Compared with RAW267.4 cells, γ-TE shows similar or stronger inhibitory effects on LPS-triggered activation of NF-κB, C/EPBβ and C/EBPδ, and more potently suppresses IL-6 and G-CSF in bone marrow-derived macrophages. Our study demonstrates that γ-TE has anti-inflammatory activities by inhibition of NF-κB and C/EBPs activation in macrophages.
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DOI：
10.4049/jimmunol.0802971
发表时间：
2009-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu YC;Kim I;Lye E;Shen F;Suzuki N;Suzuki S;Gerondakis S;Akira S;Gaffen SL;Yeh WC;Ohashi PS
通讯作者：
Ohashi PS
影响因子：
11.4
作者：
AKIRA, S;ISSHIKI, H;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
影响因子：
4.7
作者：
Mahalingam, D.;Radhakrishnan, A. K.;Nesaretnam, K.
通讯作者：
Nesaretnam, K.
DOI：
10.1073/pnas.200357097
发表时间：
2000-10-10
影响因子：
11.1
作者：
Jiang, Q;Elson-Schwab, I;Ames, BN
通讯作者：
Ames, BN
影响因子：
4.4
作者：
Grishin, AV;Wang, J;Ford, HR
通讯作者：
Ford, HR