LincRNA-Cox2 Regulates Smoke-induced Inflammation in Murine Macrophages.
LincRNA-Cox2 Regulates Smoke-induced Inflammation in Murine Macrophages.
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LincRNA-Cox2 调节小鼠巨噬细胞中烟雾引起的炎症。
DOI：
10.1165/rcmb.2022-0413oc
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发表时间：
2023
影响因子：
6.4
通讯作者：
Carpenter,Susan
中科院分区：
文献类型：
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作者：
Salih,MaysMohammed;Robinson,ElektraKantzari;Malekos,Eric;Perez,Elizabeth;Capili,Allyson;Kim,Kihwan;Zhang,WilliamZ;Cloonan,SuzanneM;Carpenter,Susan
香烟烟雾（CS）暴露是许多慢性疾病的危险因素，包括慢性阻塞性肺疾病，但烟雾暴露改变体内平衡并导致慢性炎症的机制知之甚少。在这里，我们展示了烟雾在调节长非编码RNA中的一个新作用，表明它激活了incRNA-Cox 2，我们以前认为它在炎症调节中起作用。将lincRNA-Cox 2小鼠模型暴露于体内吸烟证实lincRNA-Cox 2作为炎症基因表达的调节因子，对全身和肺内的吸烟作出反应。我们还报道了lincRNA-Cox 2在暴露于LPS刺激的烟熏骨髓源性巨噬细胞中负调控基因。除了对长链非编码RNA的影响外，我们还报道了CS在体内给药后骨髓小生境中炎症蛋白编码基因的转录和剪接失调。总的来说，这项工作提供了从基因表达到剪接的先天免疫信号传导如何在体内暴露于CS后改变的见解，并强调了lincRNA-Cox 2在烟雾暴露后调节免疫基因中的重要新作用。
Cigarette smoke (CS) exposure is a risk factor for many chronic diseases, including chronic obstructive pulmonary disease, but the mechanism by which smoke exposure can alter homeostasis and bring about chronic inflammation is poorly understood. Here, we showcase a novel role for smoke in regulating long noncoding RNAs, showing that it activateslincRNA-Cox2, which we previously characterized as functional in inflammatory regulation. ExposinglincRNA-Cox2murine models to smokein vivoconfirmedlincRNA-Cox2as a regulator of inflammatory gene expression in response to smoke both systemically and within the lung. We also report thatlincRNA-Cox2negatively regulates genes in smoked bone marrow–derived macrophages exposed to LPS stimulation. In addition to the effects on long noncoding RNAs, we also report dysregulated transcription and splicing of inflammatory protein-coding genes in the bone marrow niche after CS exposurein vivo. Collectively, this work provides insights into how innate immune signaling from gene expression to splicing is altered afterin vivoexposure to CS and highlights an important new role forlincRNA-Cox2in regulating immune genes after smoke exposure.