Inflammatory cytokines regulate microRNA-155 expression in human retinal pigment epithelial cells by activating JAK/STAT pathway.
Inflammatory cytokines regulate microRNA-155 expression in human retinal pigment epithelial cells by activating JAK/STAT pathway.
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DOI：
10.1016/j.bbrc.2010.10.042
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发表时间：
2010-11-12
影响因子：
3.1
通讯作者：
Redmond TM
中科院分区：
文献类型：
--
作者：
Kutty RK;Nagineni CN;Samuel W;Vijayasarathy C;Hooks JJ;Redmond TM
视网膜色素上皮的炎症反应在视网膜退行性疾病如老年性黄斑变性的发病机制中起关键作用。我们之前的研究表明，从成人供体眼中建立的人视网膜色素上皮细胞（HRPE）通过增强许多细胞因子和趋化因子的表达来响应炎症细胞因子。为了研究microRNA （miRNA）在调节这种反应中的作用，我们对暴露于炎症细胞因子组合（IFN-γ + TNF-α + IL-1β）的HRPE细胞中的miRNA表达进行了微阵列分析。芯片分析显示miR-155的表达增加了约11倍，通过实时PCR分析证实了这一点。单独用IFN-γ、TNF-α或IL-1β处理细胞时，miR-155的表达增强，但联合使用这些细胞因子会夸大这种作用。炎症细胞因子miR-155表达的增加与STAT1激活的增加以及与MIR155基因启动子区域中假定的STAT1结合元件的蛋白质结合的增加有关。这些活性均被JAK抑制剂1有效阻断。我们的研究结果表明，炎症细胞因子通过激活JAK/STAT信号通路增加miR-155在人视网膜色素上皮细胞中的表达。
Inflammatory response of the retinal pigment epithelium plays a critical role in the pathogenesis of retinal degenerative diseases such as age-related macular degeneration. Our previous studies have shown that human retinal pigment epithelial (HRPE) cells, established from adult donor eyes, respond to inflammatory cytokines by enhancing the expression of a number of cytokines and chemokines. To investigate the role of microRNA (miRNA) in regulating this response, we performed microarray analysis of miRNA expression in HRPE cells exposed to inflammatory cytokine mix (IFN-γ + TNF-α + IL-1β). Microarray analysis revealed ~11-fold increase in miR-155 expression, which was validated by real-time PCR analysis. The miR-155 expression was enhanced when the cells were treated individually with IFN-γ, TNF-α or IL-1β, but combinations of the cytokines exaggerated the effect. The increase in miR-155 expression by the inflammatory cytokines was associated with an increase in STAT1 activation as well as an increase in protein binding to putative STAT1 binding elements present in the MIR155 gene promoter region. All these activities were effectively blocked by JAK inhibitor 1. Our results show that the inflammatory cytokines increase miR-155 expression in human retinal pigment epithelial cells by activating the JAK/STAT signaling pathway.
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影响因子：
5.4
作者：
Skalsky, Rebecca L.;Samols, Mark A.;Renne, Rolf
通讯作者：
Renne, Rolf
影响因子：
--
作者：
Stanczyk, Joanna;Pedrioli, Deena A. Leslie;Kyburz, Diego
通讯作者：
Kyburz, Diego
影响因子：
--
作者：
Cousins, SW;Espinosa-Heidmann, DG;Csaky, KG
通讯作者：
Csaky, KG
影响因子：
3.7
作者：
Schmid CD;Bucher P
通讯作者：
Bucher P
DOI：
10.1073/pnas.0500613102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Eis, PS;Tam, W;Dahlberg, JE
通讯作者：
Dahlberg, JE