Mai Jietang, Virtue Anthony, Maley Erin, Tran Tran, Yin Ying, Meng Shu, Pansuria Meghana, Jiang Xiaohua, Wang Hong, Yang Xiao-Feng
Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Front Biosci (Elite Ed). 2012 Jan 1;4(4):1478-95. doi: 10.2741/e474.
Interleukin-17 cytokines are a family of pro-inflammatory cytokines. Our current studies found: i) IL-17 cytokines are not ubiquitously expressed, but several receptors and TRAF3IP2 are ubiquitously expressed in tissues with a few exceptions; ii) heart and vascular tissue are in the second tier of readiness to respond to IL-17 cytokine stimulation; iii) alternative transcription starting sites and alternative spliced isoforms are found in IL-17 cytokine and receptor transcripts; iv) higher hypomethylation status is associated with higher expressions of IL-17 receptors; v) the binding sites of several RNA binding proteins are found in the 3'UTRs of the mRNAs of IL-17 cytokines and receptors; and vi) numerous microRNA binding sites are statistically equivalent to that of experimentally verified microRNAs-mRNA interactions in the 3'UTRs of IL-17 cytokine and receptor mRNAs. These results suggest that mechanisms including alternative promoters, alternative splicing, RNA binding proteins, and microRNAs regulate the structures and expressions of IL-17 cytokines and receptors. These results provide an insight into the roles of IL-17 in mediating inflammation and immunity.
白细胞介素-17细胞因子是一类促炎细胞因子。我们目前的研究发现:i)白细胞介素-17细胞因子并非在所有组织中都有表达,但有少数例外情况,其几种受体和TRAF3IP2在组织中广泛表达;ii)心脏和血管组织对白细胞介素-17细胞因子刺激的反应处于第二级准备状态;iii)在白细胞介素-17细胞因子和受体转录本中发现了可变转录起始位点和可变剪接异构体;iv)较高的低甲基化状态与白细胞介素-17受体的高表达相关;v)在白细胞介素-17细胞因子和受体mRNA的3'UTR中发现了几种RNA结合蛋白的结合位点;vi)在白细胞介素-17细胞因子和受体mRNA的3'UTR中,大量微小RNA结合位点在统计学上与经实验验证的微小RNA-mRNA相互作用相当。这些结果表明,包括可变启动子、可变剪接、RNA结合蛋白和微小RNA在内的机制调节白细胞介素-17细胞因子和受体的结构与表达。这些结果为白细胞介素-17在介导炎症和免疫中的作用提供了深入了解。