Silencing ROCK1 ameliorates ventilator-induced lung injury in mice by inhibiting macrophages' NLRP3 signaling.

Rho kinase, including two subtypes, ROCK1 and ROCK2, controls a variety of biological processes helping coordinate the tissues response to stress and injury. Some authors believe that alveolar macrophages (AMs) play a key role in the early phase of ventilator-induced lung injury (VILI), which is closely related to the activation of NLRP3 inflammasome and NF-κB signaling. However, there is currently little known about the relationship between ROCK signaling and NLRP3 inflammasome. Accordingly, we focused on exploring the effect of ROCK for NLRP3 inflammasome, the results showed that VILI in C57BL/6 mice significantly increased NF-κB, NLRP3, ASC, caspase1 expression, and the secretion of cytokines, which was reversed by applying the ROCK Inhibitor-Y27632. Moreover, the use of AMs and mechanical stretching suggested that ROCK regulated transcriptional level of NF-κB and NLRP3 inflammasome in AMs. Specifically, we silenced the ROCK1 and ROCK2 respectively, and found that the inflammation of MH-S cells after LPS and ATP priming could be regulated by ROCK1 and ROCK2, while the NLRP3 was only dependent upon ROCK1. Meantime, the related genes of NLRP3 signal are also regulated by ROCK1. Collectively, our data suggest that silencing ROCK1 ameliorates VILI in mice in part by inhibiting AMs' NLRP3 signaling pathway.