PIM2 deletion alleviates lipopolysaccharide (LPS)-induced respiratory distress syndrome (ARDS) by suppressing NLRP3 inflammasome.

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.

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