Advanced glycation end products attenuate the function of tumor necrosis factor-like weak inducer of apoptosis to regulate the inflammatory response
Advanced glycation end products attenuate the function of tumor necrosis factor-like weak inducer of apoptosis to regulate the inflammatory response
复制标题
晚期糖基化终末产物减弱肿瘤坏死因子样弱凋亡诱导剂调节炎症反应的功能
DOI：
10.1007/s11010-017-3045-6
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发表时间：
2017
影响因子：
4.3
通讯作者：
Mori S
中科院分区：
文献类型：
--
作者：
Watanabe M;Toyomura T;Wake H;Liu K;Teshigawara K;Takahashi H;Nishibori M;Mori S
晚期糖基化终产物（Advanced glycation end products，AGEs）是由还原糖或其代谢产物与多种生物分子的游离氨基发生非酶促糖基化反应而形成的，在多种炎症性疾病中发挥着重要的病理生理作用。在早期的研究中，认为肿瘤坏死因子样弱凋亡诱导剂（TWEAK）在调节肿瘤坏死因子α（TNFα）诱导的炎症反应中具有独特的作用。在这项研究中，我们研究了AGEs-TWEAK相互作用对内皮细胞促炎信号反应的影响，以及AGEs对TWEAK在炎症过程中的细胞功能的影响。用实时荧光定量RT-PCR检测AGEs对TWEAK/TNFα诱导的内皮样EA.hy.926细胞白细胞介素8（IL-8）基因表达的影响。使用重组His标记的TWEAK和AGEs进行下拉测定。用经典和非经典途径特异性抗体通过Western印迹分析NF-κB活化。AGEs剂量依赖性地抑制TWEAK诱导的IL-8基因表达，而AGEs本身对IL-8表达几乎没有影响。在下拉试验中发现AGEs直接与TWEAK结合。TWEAK预处理抑制TNFα诱导的IL-8产生和经典NF-κB活化，而TWEAK诱导的非经典NF-κB活化则被预处理增强。TWEAK预处理引起的这些效应被AGEs的共同加入所消除。这些结果提示AGEs可减弱TWEAK对TNFα诱导的炎症反应的调节作用，为进一步了解AGEs与TWEAK的相互作用在炎症过程中的意义提供了重要线索。
Advanced glycation end products (AGEs) are formed from the non-enzymatic glycation reaction of reducing sugars or their metabolites with the free amino groups of several biomolecules and are known to play pathophysiological roles in various inflammatory diseases. In an earlier study, it was suggested that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has a unique role to regulate the tumor necrosis factor α (TNFα)-induced inflammatory response. In this study, we investigated the effect of the AGEs–TWEAK interaction on proinflammatory signaling responses in endothelial cells and the influence of AGEs on the cellular function of TWEAK in the inflammatory process. The effect of AGEs on the TWEAK/TNFα-induced gene expression of interleukin-8 (IL-8) was determined by real-time RT-PCR in endothelial-like EA.hy.926 cells. The pull-down assay was performed using recombinant His-tagged TWEAK and AGEs. The NF-κB activation was analyzed by Western blotting with canonical and non-canonical pathway-specific antibodies. AGEs dose-dependently inhibited TWEAK-induced IL-8 gene expression, whereas AGEs themselves had almost no effect on IL-8 expression. AGEs were found to bind directly to TWEAK in the pull-down assay. TNFα-induced IL-8 production and canonical NF-κB activation were suppressed by TWEAK pretreatment, whereas TWEAK-induced non-canonical NF-κB activation was enhanced by pretreatment. These effects induced by TWEAK pretreatment were abolished by the co-addition of AGEs. Our findings suggest that AGEs attenuate the function of TWEAK to regulate the TNFα-induced inflammatory responses, which provide important clues for understanding the significance of the AGEs–TWEAK interaction in inflammatory processes.
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DOI：
10.1111/j.1440-1746.2007.04943.x
发表时间：
2007-07-01
影响因子：
4.1
作者：
Hyogo, Hideyuki;Yamagishi, Sho-ichi;Tazuma, Susumu
通讯作者：
Tazuma, Susumu
影响因子：
15.9
作者：
Febbraio, M;Podrez, EA;Silverstein, RL
通讯作者：
Silverstein, RL
影响因子：
5.5
作者：
Simon-Muela, Inmaculada;Llaurado, Gemma;Megia, Ana
通讯作者：
Megia, Ana
影响因子：
5.7
作者：
Takeuchi, M;Makita, Z;Kameda, Y
通讯作者：
Kameda, Y
在类风湿性关节炎成纤维细胞样滑膜细胞中，TWEAK-Fn14 相互作用抑制 TNF 诱导的 IL-6。
影响因子：
4.3
作者：
J. Yamana;E. Morand;Tsuno Manabu;Katsue Sunahori;Kouji Takasugi;H. Makino;M. Yamamura
通讯作者：
M. Yamamura