Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei, People's Republic of China.
Department of Biochemistry and Molecular Biology, Medical College, Hubei Minzu University, Enshi 445000, Hubei, People's Republic of China.
J Immunol. 2019 Sep 15;203(6):1548-1559. doi: 10.4049/jimmunol.1900256. Epub 2019 Aug 5.
Long noncoding RNAs are important regulators of gene expression in innate immune responses. Antisense IL-7 (IL-7-AS) is a newly discovered long noncoding RNA in human and mouse that has been reported to regulate the expression of IL-6. However, the potential function of IL-7-AS in innate immune system is not fully understood. In this study, we found that the expression of IL-7-AS is primarily dependent on the NF-κB and MAPK signaling pathways in macrophages and intestinal epithelial cells. Functionally, IL-7-AS promotes the expression of several inflammatory genes, including , , , and , in cells in response to LPS. Specifically, IL-7-AS physically interacts with p300 to regulate histone acetylation levels around the promoter regions of these gene loci. Moreover, IL-7-AS and p300 complex modulate the assembly of SWI/SNF complex to the promoters. IL-7-AS regulates chemotaxis activity of monocytes to intestine epithelial cells with involvement of CCL2. Therefore, our data indicate a new promoting role for NF-κB/MAPK-responsive IL-7-AS in the transcriptional regulation of inflammatory genes in the innate immune system although modulation of histone acetylation around the promoters of related genes.
长非编码 RNA 是先天免疫反应中基因表达的重要调节因子。反义 IL-7(IL-7-AS)是在人和小鼠中发现的一种新的长非编码 RNA,据报道它可以调节 IL-6 的表达。然而,IL-7-AS 在先天免疫系统中的潜在功能尚未完全阐明。在本研究中,我们发现 IL-7-AS 的表达主要依赖于巨噬细胞和肠上皮细胞中的 NF-κB 和 MAPK 信号通路。在功能上,IL-7-AS 可促进 LPS 刺激细胞中几种炎症基因的表达,包括 、 、 和 。具体而言,IL-7-AS 与 p300 相互作用,调节这些基因座启动子区域周围的组蛋白乙酰化水平。此外,IL-7-AS 和 p300 复合物调节 SWI/SNF 复合物到启动子的组装。IL-7-AS 通过涉及 CCL2 的方式调节单核细胞向肠上皮细胞的趋化活性。因此,我们的数据表明,NF-κB/MAPK 反应性 IL-7-AS 在先天免疫系统中炎症基因的转录调节中发挥新的促进作用,尽管它调节了相关基因启动子周围的组蛋白乙酰化。