Qian Na, Distefano Rebecca, Ilieva Mirolyuba, Madsen Jens Hedelund, Rennie Sarah, Uchida Shizuka
Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, DK-2450 Copenhagen SV, Denmark.
Noncoding RNA. 2023 Aug 25;9(5):50. doi: 10.3390/ncrna9050050.
The NLRP3 inflammasome plays a pivotal role in regulating inflammation and immune responses. Its activation can lead to an inflammatory response and pyroptotic cell death. This is beneficial in the case of infections, but excessive activation can lead to chronic inflammation and tissue damage. Moreover, while most of the mammalian genome is transcribed as RNAs, only a small fraction codes for proteins. Among non-protein-coding RNAs, long non-coding RNAs (lncRNAs) have been shown to play key roles in regulating gene expression and cellular processes. They interact with DNA, RNAs, and proteins, and their dysregulation can provide insights into disease mechanisms, including NLRP3 inflammasome activation. Here, we systematically analyzed previously published RNA sequencing (RNA-seq) data of NLRP3 inflammasome activation in monocytes/macrophages to uncover inflammasome-regulated lncRNA genes. To uncover the functional importance of inflammasome-regulated lncRNA genes, one inflammasome-regulated lncRNA, , was knocked down in an in vitro model of macrophage polarization. The results indicate that silencing of resulted in the up-regulation tumor necrosis factor (), suggesting that this lncRNA might be involved in pro-inflammatory response in macrophages. To make our analyzed data more accessible, we developed the web database InflammasomeDB.
NLRP3炎性小体在调节炎症和免疫反应中起关键作用。其激活可导致炎症反应和细胞焦亡。在感染情况下这是有益的，但过度激活会导致慢性炎症和组织损伤。此外，虽然大多数哺乳动物基因组转录为RNA，但只有一小部分编码蛋白质。在非蛋白质编码RNA中，长链非编码RNA（lncRNA）已被证明在调节基因表达和细胞过程中起关键作用。它们与DNA、RNA和蛋白质相互作用，其失调可为疾病机制提供见解，包括NLRP3炎性小体激活。在这里，我们系统地分析了先前发表的单核细胞/巨噬细胞中NLRP3炎性小体激活的RNA测序（RNA-seq）数据，以发现炎性小体调节的lncRNA基因。为了揭示炎性小体调节的lncRNA基因的功能重要性，在巨噬细胞极化的体外模型中敲低了一种炎性小体调节的lncRNA， 。结果表明， 的沉默导致肿瘤坏死因子（ ）上调，表明这种lncRNA可能参与巨噬细胞中的促炎反应。为了使我们分析的数据更易于获取，我们开发了网络数据库InflammasomeDB。
