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Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard
Annals of the New York Academy of Sciences ( IF 5.2 ) Pub Date : 2020-08-06 , DOI: 10.1111/nyas.14444
L Cody Smith 1 , Alessandro Venosa 2 , Andrew J Gow 1 , Jeffrey D Laskin 3 , Debra L Laskin 1
Affiliation  

Nitrogen mustard (NM) and sulfur mustard are cytotoxic alkylating agents that cause severe and progressive damage to the respiratory tract. Evidence indicates that macrophages play a key role in the acute inflammatory phase and the later resolution/profibrotic phase of the pathogenic response. These diverse roles are mediated by inflammatory macrophages broadly classified as M1 proinflammatory and M2 anti‐inflammatory that sequentially accumulate in the lung in response to injury. The goal of the present study was to identify signaling mechanisms contributing to macrophage activation in response to mustards. To accomplish this, we used RNA sequencing to analyze the gene expression profiles of lung macrophages isolated 1 and 28 days after intratracheal exposure of rats to NM (0.125 mg/kg) or phosphate‐buffered saline control. We identified 641 and 792 differentially expressed genes 1 and 28 days post‐NM exposure, respectively. These genes are primarily involved in processes related to cell movement and are regulated by cytokines, including tumor necrosis factor‐α, interferon‐γ, and interleukin‐1β. Some of the most significantly enriched canonical pathways included STAT3 and NF‐κB signaling. These cytokines and pathways may represent potential targets for therapeutic intervention to mitigate mustard‐induced lung toxicity.

中文翻译:

氮芥诱导肺损伤过程中肺巨噬细胞的转录谱

氮芥 (NM) 和硫芥是细胞毒性烷化剂,可对呼吸道造成严重且渐进的损害。有证据表明,巨噬细胞在急性炎症期和病原反应的后期消退/促纤维化阶段中起着关键作用。这些不同的作用是由炎性巨噬细胞介导的,这些巨噬细胞被广泛归类为 M1 促炎细胞和 M2 抗炎细胞,它们在肺中依次积累以响应损伤。本研究的目标是确定有助于巨噬细胞激活以响应芥末的信号机制。为此,我们使用 RNA 测序来分析大鼠气管内暴露于 NM (0.125 mg/kg) 或磷酸盐缓冲盐水对照后 1 天和 28 天分离的肺巨噬细胞的基因表达谱。我们分别在 NM 暴露后 1 天和 28 天鉴定了 641 和 792 个差异表达的基因。这些基因主要参与与细胞运动相关的过程,并受细胞因子调节,包括肿瘤坏死因子-α、干扰素-γ和白细胞介素-1β。一些最显着丰富的经典途径包括 STAT3 和 NF-κB 信号。这些细胞因子和通路可能代表治疗干预的潜在目标,以减轻芥子气诱导的肺毒性。
更新日期:2020-08-06
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