Macrophages (Mϕ) are an important component of the innate immune system; they play critical roles in the first line of defense to pathogen invasion and modulate adaptive immunity. MicroRNAs (miRNAs) are a newly recognized, important level of gene expression regulation. However, their roles in the regulation of Mϕ and the immune system are still not fully understood. In this report, we provide evidence that the conserved miR-183/96/182 cluster (miR-183/96/182) modulates Mϕ function in their production of reactive nitrogen (RNS) and oxygen species (ROS) and their inflammatory response to Pseudomonas aeruginosa (PA) infection and/or lipopolysaccharide (LPS) treatment. We show that knockdown of miR-183/96/182 results in decreased production of multiple proinflammatory cytokines in response to PA or LPS treatment in Mϕ-like Raw264.7 cells. Consistently, peritoneal Mϕ from miR-183/96/182-knockout versus wild-type mice are less responsive to PA or LPS, although their basal levels of proinflammatory cytokines are increased. In addition, overexpression of miR-183/96/182 results in decreased production of nitrite and ROS in Raw264.7 cells. We also provide evidence that DAP12 and Nox2 are downstream target genes of miR-183/96/182. These data suggest that miR-183/96/182 imposes global regulation on various aspects of Mϕ function through different downstream target genes.

中文翻译：

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miR-183/96/182 簇调节巨噬细胞功能以响应铜绿假单胞菌。

巨噬细胞（Mφ）是先天免疫系统的重要组成部分；它们在病原体入侵和调节适应性免疫的第一道防线中发挥关键作用。MicroRNAs (miRNAs) 是一种新发现的重要的基因表达调控水平。然而，它们在调节 Mφ 和免疫系统中的作用仍未完全了解。在本报告中，我们提供证据表明保守的 miR-183/96/182 簇 (miR-183/96/182) 在其产生活性氮 (RNS) 和氧物质 (ROS) 及其炎症反应中调节 Mφ 功能。铜绿假单胞菌 (PA) 感染和/或脂多糖 (LPS) 治疗。我们显示 miR-183/96/182 的敲低导致在 Mφ 样 Raw264.7 细胞中响应 PA 或 LPS 处理的多种促炎细胞因子的产生减少。始终如一，与野生型小鼠相比，来自 miR-183/96/182 敲除的腹膜 Mφ 对 PA 或 LPS 的反应较低，尽管它们的促炎细胞因子的基础水平有所增加。此外，miR-183/96/182 的过表达导致 Raw264.7 细胞中亚硝酸盐和 ROS 的产生减少。我们还提供证据表明 DAP12 和 Nox2 是 miR-183/96/182 的下游靶基因。这些数据表明 miR-183/96/182 通过不同的下游靶基因对 Mφ 功能的各个方面进行全局调节。我们还提供证据表明 DAP12 和 Nox2 是 miR-183/96/182 的下游靶基因。这些数据表明 miR-183/96/182 通过不同的下游靶基因对 Mφ 功能的各个方面进行全局调节。我们还提供证据表明 DAP12 和 Nox2 是 miR-183/96/182 的下游靶基因。这些数据表明 miR-183/96/182 通过不同的下游靶基因对 Mφ 功能的各个方面进行全局调节。