Toll-like Receptor 4-mediated Immunoregulation by the Aqueous Extract of Mori Fructus

被引:20
|
作者
Yang, Xin-Ying [1 ]
Park, Gil-Soon [1 ]
Lee, Moo Hyung [1 ]
Chang, In Ae [1 ]
Kim, Youn Chul [2 ]
Kim, Sung Yeon [2 ]
Lee, Joo Young [3 ]
Yun, Yong Gab [4 ]
Park, Hyun [1 ]
机构
[1] Wonkwang Univ, Sch Med, Dept Infect Biol, Zoonosis Res Ctr, Iksan 570749, Chonbuk, South Korea
[2] Wonkwang Univ, Coll Pharm, Iksan 570749, Chonbuk, South Korea
[3] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea
[4] Wonkwang Univ, Dept Oriental Med, Iksan 570749, Chonbuk, South Korea
关键词
Mori Fructus; nitric oxide; TNF-alpha; IFN-gamma; TLR4; Th1 immune response; NF-KAPPA-B; PROPRIETARY EXTRACT; SIGNAL-TRANSDUCTION; REACTIVE OXYGEN; CELLS; MACROPHAGES; EXPRESSION; PATHWAYS; LPS;
D O I
10.1002/ptr.2818
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The aqueous extract of Mori Fructus (MF) exerts a change of phenotype and a cytoprotective effect in macrophages. The present study was carried out to investigate the immunomodulating activity of MF on the expression of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), co-stimulatory molecules and also interferon-gamma (IFN-gamma) in macrophages and splenocytes. Toll-like receptor 4 (TLR4) is a promising molecular target for immune-modulating drugs. It was hypothesized that one possible upstream signaling pathway leading to immuno-regulation of MF may be mediated by TLRs. Multiple signaling molecules (NF-kappa B, ERK1/2, p38 and JNK) of the TLR4 signaling pathway were also detected. It was found that MF increased NO production and TNF-a secretion in RAW 264.7 and peritoneal macrophages, co-stimulatory molecules expression in peritoneal macrophages and IFN-gamma expression in splenocytes. Further studies indicated that MF could significantly induce the phosphorylation of signal molecules of MAPKs and the degradation of I kappa B alpha which finally led to the activation and nuclear translocation of nuclear factor-kappa B (NF-kappa B) for the target gene expression. All those notions disclosed that the aqueous extract MF is a new TLR4 activator, which induces a Th1 immune response as a consequence of induction of cytokines secretion, especially TNF-alpha and IFN-gamma. Copyright 2009 John Wiley & Sons, Ltd.
引用
收藏
页码:1713 / 1720
页数:8
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