MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection.
MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection.
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DOI：
10.1016/j.ijpara.2010.11.011
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发表时间：
2011-03
影响因子：
4
通讯作者：
Chen XM
中科院分区：
文献类型：
--
作者：
Gong AY;Hu G;Zhou R;Liu J;Feng Y;Soukup GA;Chen XM
微小隐孢子虫是一种原生动物寄生虫，感染胃肠道上皮细胞，在全球范围内引起人和动物的腹泻疾病。微小隐孢子虫感染后的病理变化包括隐窝增生，这是一种轻度炎症反应，淋巴细胞渗入到肠粘膜中。细胞间黏附分子-1(ICAM-1)等黏附分子在感染的上皮细胞表面的表达可能促进感染部位淋巴细胞的黏附和识别。MicroRNAs(MiRNAs)是由23个核苷酸组成的小RNA分子，通过翻译抑制或mRNA降解来负向调节编码蛋白质的基因的表达。我们最近报道，microRNA-221(miR-221)通过靶向ICAM-1 3‘-非翻译区(UTR)来调节ICAM-1的翻译。在这项研究中，我们利用人胆道隐孢子虫病的体外模型，测试了miR-221在调节微小隐孢子虫感染的上皮细胞ICAM-1表达中的作用。微小隐孢子虫感染后，上皮细胞ICAM-1在消息和蛋白水平均有上调。用放线菌素D抑制ICAM-1转录只能在蛋白水平部分阻断微小隐孢子虫诱导的ICAM-1表达。微小隐孢子虫感染可降低感染上皮细胞miR-221的表达。当用覆盖ICAM-1 3‘-UTR中miR-221结合位点的荧光素酶报告基因转染细胞，然后暴露于微小隐孢子虫时，可检测到荧光素酶活性增强。MiR-221前体基因的转染可抑制微小隐孢子虫刺激的ICAM-1蛋白表达。此外，ICAM-1在感染的上皮细胞上的表达促进了共培养的Jurkat细胞的上皮黏附。这些结果表明，miR-221介导的翻译抑制控制了上皮细胞对微小弧菌感染的ICAM-1的表达。
Cryptosporidium parvum is a protozoan parasite that infects gastrointestinal epithelial cells and causes diarrheal disease in humans and animals globally. Pathological changes following C. parvum infection include crypt hyperplasia, a modest inflammatory reaction with increased infiltration of lymphocytes into intestinal mucosa. Expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), on infected epithelial cell surfaces may facilitate adhesion and recognition of lymphocytes at infection sites. MicroRNAs (miRNAs) are small RNA molecules of 23 nucleotides that negatively regulate protein-coding gene expression via translational suppression or mRNA degradation. We recently reported that microRNA-221 (miR-221) regulates ICAM-1 translation through targeting the ICAM-1 3′-untranslated region (UTR). In this study, we tested the role of miR-221 in regulating ICAM-1 expression in epithelial cells in response to C. parvum infection using an in vitro model of human biliary cryptosporidiosis. Up-regulation of ICAM-1 at both message and protein levels was detected in epithelial cells following C. parvum infection. Inhibition of ICAM-1 transcription with actinomycin D could only partially block C. parvum-induced ICAM-1 expression at the protein level. Cryptosporidium parvum infection decreased miR-221 expression in infected epithelial cells. When cells were transfected with a luciferase reporter construct covering the miR-221 binding site in the ICAM-1 3′-UTR and then exposed to C. parvum, an enhanced luciferase activity was detected. Transfection of miR-221 precursor abolished C. parvum-stimulated ICAM-1 protein expression. In addition, expression of ICAM-1 on infected epithelial cells facilitated epithelial adherence of co-cultured Jurkat cells. These results indicate that miR-221-mediated translational suppression controls ICAM-1 expression in epithelial cells in response to C. parvum infection.
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影响因子：
11.8
作者：
Guerrant RL
通讯作者：
Guerrant RL
DOI：
10.1086/648589
发表时间：
2010-01-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Gong AY;Zhou R;Hu G;Liu J;Sosnowska D;Drescher KM;Dong H;Chen XM
通讯作者：
Chen XM
影响因子：
3.1
作者：
Lacroix, S;Mancassola, R;Laurent, F
通讯作者：
Laurent, F
多种 TLRs 在人胆管细胞中表达，并通过激活 NF-κB 介导宿主上皮细胞对副隐孢子虫的防御反应
影响因子：
4.4
作者：
Chen, XM;O'Hara, SP;LaRusso, NF
通讯作者：
LaRusso, NF
DOI：
10.1152/ajpgi.00490.2009
发表时间：
2010-04-01
影响因子：
4.5
作者：
Hu, Guoku;Gong, Ai-Yu;Chen, Xian-Ming
通讯作者：
Chen, Xian-Ming