Lincenc1 regulates the lipopolysaccharide-induced inflammatory response in macrophages

摘要/摘要 革兰氏阴性（G-）细菌经常在宿主中诱导压倒性的炎症反应。尽管多年 研究表明，G-细菌感染后炎症反应的调节仍不清楚，因此， 阻碍了新的治疗/诊断策略的发展。哺乳动物基因组编码数千个 长链非编码RNA（lncRNA）LncRNA在各种免疫细胞中广泛表达，包括 单核细胞和巨噬细胞。已报道lncRNA参与多种生物过程， 包括基因表达调控、剂量补偿和基因组学印记，但作为 然而，很少有研究探索它们如何改变宿主期间的细胞分化/功能， 病原体相互作用我们发现Lincenc 1在小鼠肺中被显著诱导， 感染G-细菌或暴露于LPS后，G-细菌外膜的丰富糖脂 细菌此外，我们的体外数据表明，Lincenc 1在巨噬细胞中被诱导，但在其他细胞中不被诱导， 如上皮细胞和嗜中性粒细胞。在功能上，Lincenc 1促进了 巨噬细胞和炎性细胞因子的分泌。在这里，我们提出lncRNA Lincenc 1促进 G-细菌/LPS通过激活肺泡巨噬细胞诱导肺部炎症。为了验证这个假设，我们 具体目的一：研究Lincenc 1在巨噬细胞中的作用， 体外活化。具体目的2：研究Lincenc 1在体内肺部炎症中的作用。成功 所提出的目标的完成将揭示Lincenc 1在G-细菌感染中的作用。本研究 这可能有助于确定肺部炎症和损伤的新机制和/或治疗策略。

Summary/Abstract Gram-negative (G-) bacteria frequently induce an overwhelming inflammatory response in hosts. Despite years of research, the regulation of the inflammatory response after G- bacterial infection remains unclear, thus impeding the development of novel therapeutic/diagnostic strategies. Mammalian genomes encode thousands of long non-coding RNAs (lncRNAs). LncRNAs are extensively expressed in various immune cells including the monocytes, and macrophages. The lncRNAs have been reported to be involved in diverse biological processes, including the regulation of the expression of genes, the dosage compensation and genomics imprinting, but as yet very less research has been carried out to explore how they alter cell differentiation/function during host- pathogens interactions. We found that Lincenc1 is strikingly induced in the lungs obtained from the mice infected with G- bacteria or after exposure to LPS, an abundant glycolipid of the outer membrane of G- bacteria. Furthermore, our in vitro data suggest that Lincenc1 is induced in macrophages but not in other cells, such as the epithelial cells and neutrophils. Functionally, Lincenc1 promotes the classical activation of macrophages and the secretion of inflammatory cytokines. Here we propose that lncRNA Lincenc1 promotes G- bacterial/LPS induced lung inflammation via activating alveolar macrophages. To test this hypothesis, we propose the following two specific aims: Specific Aim I: To investigate the role of Lincenc1 in macrophage activation in vitro. Specific Aim 2: To investigate the role of Lincenc1 in lung inflammation in vivo. Successful completion of the proposed aims will uncover the role of Lincenc1 in G- bacterial infections. This study potentially will help to identify novel mechanisms and/or therapeutic strategies for lung inflammation and injury.