Enhancement of endotoxin activity by muramyldipeptide.
Enhancement of endotoxin activity by muramyldipeptide.
复制标题
胞壁酰二肽增强内毒素活性。
DOI：
--
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Shuhua Yang
中科院分区：
文献类型：
--
作者：
H. Takada;S. Yokoyama;Shuhua Yang
合成胞壁酰二肽（MDP）是细菌肽聚糖的最小结构部分，用于佐剂和相关活性，使小鼠对脂多糖（LPS）诱导的两种类型的致死性休克敏感：早期过敏性休克和晚期内毒素休克。在有关的后期反应在MDP引发的小鼠，增强生产的炎症细胞因子诱导响应各种细菌成分。MDP不仅在胃肠外给药时，而且通过口服途径给药时，在小鼠中显示出引发效应。MDP以CD 14-、Toll样受体2（TLR 2）-和TLR 4-非依赖性方式激活人单核细胞THP-1细胞，以增加MyD 88（TLR的常见衔接子和信号传导分子）的表达，并在培养的THP-1细胞中与TLR 4激动剂（LPS，合成脂质A）、TLR 2激动剂（合成脂肽）和TLR 9激动剂（细菌CpGDNA）表现出协同细胞因子诱导作用。与这些发现一致，MDP致敏的TLR 2敲除小鼠以及野生型对照，但不是TLR 4突变的C3 H/HeJ小鼠，在用合成脂质A刺激时增强肿瘤坏死因子-α的产生。与BCG和痤疮丙酸杆菌引发系统相反，MDP以干扰素-γ-非依赖性方式引发小鼠。需要进一步的研究来阐明MDP对各种细菌组分的合成和引发活性的机制。
Synthetic muramyldipeptide (MDP), the minimum structural moiety of bacterial peptidoglycan for adjuvant and related activities, sensitized mice for two types of lethal shock induced by lipopolysaccharide (LPS): an early anaphylactoid shock and late endotoxin shock. In relation to the late reaction in MDP-primed mice, enhanced production of inflammatory cytokines was induced in response to various bacterial components. MDP showed a priming effect in mice not only when administered parentally but also via the oral route. MDP activated human monocytic THP-1 cells in a CD14-, Toll-like receptor 2 (TLR2)- and TLR4-independent manner to increase expression of MyD88, a common adaptor and signaling molecule for TLRs, and exhibited synergistic cytokine inducing effects with TLR4 agonists (LPS, synthetic lipid A), TLR2 agonist (synthetic lipopeptide), and TLR9 agonist (bacterial CpGDNA) in THP-1 cells in culture. Consistent with these findings, MDP primed TLR2 knockout mice as well as wild-type controls, but not TLR4-mutated C3H/HeJ mice, to enhance production of tumor necrosis factor-alpha upon stimulation with synthetic lipid A. In contrast to the BCG- and Propionibacterium acnes-priming system, MDP primed mice in an interferon-gamma-independent manner. Further studies are required to elucidate the mechanisms of the synthetic and priming activities of MDP for various bacterial components.
DOI：
10.1073/pnas.96.25.14459
发表时间：
1999-12-07
影响因子：
11.1
作者：
Underhill, DM;Ozinsky, A;Aderem, A
通讯作者：
Aderem, A
影响因子：
4.4
作者：
T. Means;Shuyan Wang;E. Lien;A. Yoshimura;D. Golenbock;M. Fenton
通讯作者：
T. Means;Shuyan Wang;E. Lien;A. Yoshimura;D. Golenbock;M. Fenton