Hypoxia-increased RAGE expression regulates chemotaxis and pro inflammatory cytokines release through nuclear translocation of NF-κ B and HIFI α in THP-1 cells
Hypoxia-increased RAGE expression regulates chemotaxis and pro inflammatory cytokines release through nuclear translocation of NF-κ B and HIFI α in THP-1 cells
复制标题
缺氧增加的 RAGE 表达通过 THP-1 细胞中 NF-k B 和 HIF1a 的核转位调节趋化性和促炎细胞因子的释放
DOI：
10.1016/j.bbrc.2017.12.084
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发表时间：
2018-01-15
影响因子：
3.1
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
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作者：
Bai, Wei;Zhou, Jing;Zhang, Wei
低氧在调节晚期糖基化终产物受体(RAGE)表达中的潜在作用值得肯定。RAGE在低氧诱导的趋化和炎症中的作用尚不清楚。在本研究中，THP-1细胞用siRNA阻断HIFI-cc、NF-kappa B或RAGE，然后暴露于低氧(结合H_2O_2或SNP)，然后检测RAGE的表达、HIFI-cc和NF-kappa B的核转位、肿瘤坏死因子-α和IL-1β的释放以及单核细胞趋化蛋白-1和CCR2的表达。结果表明，低氧环境下THP-1细胞RAGE mRNA和蛋白表达显著增加，尤其是在含SNP或H_2O_2的溶液中。此外，SNP或H_2O_2暴露可进一步放大缺氧诱导的HIF-1α和NF-kappaB的核转位。通过siRNAs敲除HIF-1α或NF-kappa B可降低缺氧和氧化应激诱导的RAGE的高表达。用RAGE siRNA或NF-kappa B siRNA处理THP-1细胞，可以减少缺氧和氧化应激诱导的MCP-I和CCR2的表达，减少肿瘤坏死因子-α和IL-1β的释放。因此，低氧不仅通过促进核因子-kappaB和HiFiα的核转位增加THP-1细胞中RAGE的表达，而且还调节趋化和促炎细胞因子的释放，这可能部分是通过上调RAGE的表达来实现的。(C)2017 Elsevier Inc.保留所有权利。
The potential role of hypoxia in mediating the receptor for advanced glycation end products (RAGE) expression deserves to be confirmed. And the role of RAGE in hypoxia-induced chemotaxis and inflammation is still unclear. In present study, THP-1 cells were pretreated with siRNA to block HIFI cc,NF-kappa B, or RAGE, followed by exposed to hypoxia (combined with H2O2 or SNP), and then RAGE expression, nuclear translocation of HIFI cc and NF-kappa B, release of TNF-alpha and IL-1 beta, as well as expression of MCP-1 and CCR2 were measured. The results revealed that RAGE mRNA and protein in THP-1 cells were significantly increased after exposed into hypoxia atmosphere, especially into the solution containing SNP or H2O2. Moreover, SNP or H2O2 exposure could further amplify hypoxia-induced nuclear translocation of HIF-1 alpha and NF-kappa B. Knockdown HIF-1 alpha or NF-kappa B by siRNAs could reduce hypoxia-and oxidative stress-induced RAGE hyper-expression. And pretreatment THP-1 cells with RAGE siRNA or NF-kappa B siRNA could reduce hypoxia- and oxidative stress-induced expression of MCP-I and CCR2, and release of TNF-alpha and IL-1 beta. Thus, hypoxia not only increases RAGE expression in THP-1 cells by promoting nuclear translocation of NF-kappa B and HIFI alpha, but also regulates chemotaxis and pro-inflammatory cytokines release, which may be partially mediated through upregulation of RAGE expression. (C) 2017 Elsevier Inc. All rights reserved.