Inflammation has an essential role in regulating the pathogenesis of acute respiratory distress syndrome (ARDS). The serine/threonine kinase PIM2 is highly expressed in human macrophages, and exhibits regulatory role in inflammatory response. However, its effect on ARDS progression has not been investigated and still remains unclear. In the study, we attempted to investigate the potential of PIM2 during ARDS progression, and to reveal the underlying molecular mechanisms. Here, we found that PIM2 expression was dramatically up-regulated in lipopolysaccharide (LPS)-exposed murine macrophages through a dose- and time-dependent manner. Additionally, we found that PIM2 knockdown greatly alleviated LPS-triggered activation of Caspase-1, interleukin (IL)-1β, NOD-like receptor pyrin domain 3 (NLRP3) and apoptosis-associated speck-like protein (ASC) in macrophages, along with suppressed inflammatory response. Importantly, we identified that PIM2 could directly interact with NLRP3. PIM2 over-expression could further promote LPS-triggered inflammation and NLRP3 inflammasome in macrophages. Furthermore, PIM2 knockout significantly alleviated the severity of ARDS in LPS-challenged mice. Evidently decreased inflammatory response and NLRP3 inflammasome were detected in pulmonary tissues of LPS-treated mice with PIM2 deficiency. Together, our findings demonstrated that PIM2 as a promising therapeutic target for ARDS treatment through regulating NLRP3 inflammasome.

炎症在调节急性呼吸窘迫综合征（ARDS）的发病机理中起着至关重要的作用。丝氨酸/苏氨酸激酶PIM2在人类巨噬细胞中高度表达，并在炎症反应中发挥调节作用。但是，其对ARDS进展的影响尚未进行研究，仍然不清楚。在这项研究中，我们试图研究PIM2在ARDS进展过程中的潜力，并揭示其潜在的分子机制。在这里，我们发现在脂多糖（LPS）暴露的鼠巨噬细胞中，PIM2表达通过剂量和时间依赖性显着上调。此外，我们发现PIM2敲低大大减轻了LPS触发的Caspase-1，白介素（IL）-1β，巨噬细胞中的NOD样受体吡啶结构域3（NLRP3）和凋亡相关的斑点样蛋白（ASC），以及抑制的炎症反应。重要的是，我们确定PIM2可以直接与NLRP3交互。PIM2的过表达可进一步促进巨噬细胞中LPS触发的炎症和NLRP3炎性体。此外，PIM2敲除可显着减轻LPS攻击小鼠的ARDS严重程度。在LPS治疗的PIM2缺乏症小鼠的肺组织中，明显检测到炎症反应降低和NLRP3炎性体。在一起，我们的研究结果表明PIM2通过调节NLRP3炎性小体作为ARDS治疗的有希望的治疗靶点。PIM2的过表达可进一步促进巨噬细胞中LPS触发的炎症和NLRP3炎性体。此外，PIM2基因敲除可显着减轻LPS攻击小鼠的ARDS严重程度。在LPS治疗的PIM2缺乏症小鼠的肺组织中，明显检测到炎症反应降低和NLRP3炎性体。在一起，我们的研究结果表明PIM2通过调节NLRP3炎性小体作为ARDS治疗的有希望的治疗靶点。PIM2的过度表达可进一步促进巨噬细胞中LPS触发的炎症和NLRP3炎性体。此外，PIM2敲除可显着减轻LPS攻击小鼠的ARDS严重程度。在LPS治疗的PIM2缺乏症小鼠的肺组织中，明显检测到炎症反应降低和NLRP3炎性体。在一起，我们的研究结果表明PIM2通过调节NLRP3炎性小体作为ARDS治疗的有希望的治疗靶点。