HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol
HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol
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DOI：
10.1016/j.taap.2009.06.023
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发表时间：
2009-10-01
影响因子：
3.8
通讯作者：
Moon, Yuseok
中科院分区：
文献类型：
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作者：
Choi, Hye Jin;Yang, Hyun;Moon, Yuseok
HuR/Elav-like RNA binding protein 1（ELAVL 1）正调控含有AU富集元件（ARE）的转录物（如促炎细胞因子）的mRNA稳定性。核毒应激可通过增强mRNA的稳定性和转录活性来触发促炎介质的产生。我们研究了核糖毒素脱氧雪腐镰刀菌烯醇（DON）对HuR易位及其参与调节促炎性白细胞介素-8（IL-8）mRNA稳定性的影响。暴露于粘膜活性DON诱导人肠上皮细胞中内源性和外源性HuR RNA结合蛋白的核输出。干扰HuR蛋白的产生可抑制核糖核酸诱导的IL-8的分泌，并抑制其mRNA的稳定性。胞浆HuR蛋白与IL-8 mRNA相互作用，复合物的稳定性是由于转录本3 '非翻译区的存在。部分就IL-8调节转录因子而言，HuR蛋白被证明分别与DON诱导的早期生长反应基因1（EGR-1）和转录激活因子3（ATF 3）正相关和负相关。HuR是核糖毒性应激和促炎细胞因子产生之间的关键机制联系，并且对于粘膜损伤可能具有更广泛的功能意义，因为核糖毒性应激反应也在与肠道的不同环境相互作用后产生。(C)2009 Elsevier Inc. All rights reserved.
HuR/Elav-like RNA binding protein 1 (ELAVL1) positively regulates mRNA stability of AU-rich elements (ARE)-containing transcript such as pro-inflammatory cytokines. Ribotoxic stresses can trigger the production of pro-inflammatory mediators by enhancing mRNA stability and the transcriptional activity. We investigated the effects of ribotoxin deoxynivalenol (DON) on HuR translocation and its involvement in the regulation of the pro-inflammatory interleukin-8 (IL-8) mRNA stability. Exposure to the muco-active DON induced nuclear export of both endogenous and exogenous HuR RNA binding protein in human intestinal epithelial cells. the interference with HuR protein production suppressed ribotoxic DON-induced IL-8 secretionMoreover, and its mRNA stability. Cytoplasmic HuR protein interacted with IL-8 mRNA and the complex stabilization was due to the presence of 3'-untranslated region of the transcript. Partly in terms of IL-8-modulating transcription factors, HuR protein was demonstrated to be positively and negatively associated with DON-induced early growth response gene 1 (EGR-1) and activating transcription factor 3 (ATF3), respectively. HuR was a critical mechanistic link between ribotoxic stress and the pro-inflammatory cytokine production, and may have a broader functional significance with regard to mucosal insults since ribotoxic stress responses are also produced upon interactions with the diverse environment of gut. (C) 2009 Elsevier Inc. All rights reserved.