miR-16 inhibits NLRP3 inflammasome activation by directly targeting TLR4 in acute lung injury

Abstract

Acute lung injury (ALI) is the leading cause of human death, and it is widely accepted that the runaway inflammation is an important risk for the development of ALI. In the present study, we aimed to investigate the effect of miR-16 on lipopolysaccharide-induced acute lung injury in mice, especially focusing on Toll-like receptor 4 (TLR4) and NF-kB signaling pathway as well as NOD-like receptor protein 3 (NLRP3) inflammasome activation. We established in vivo and in vitro model of ALI using LPS and demonstrated that miR-16 expression was down-regulated in lung tissue as well as A549 cells after 8 h of LPS treatment. Furthermore, when miR-16 levels in lung tissues were up-regulated by miR-16 agomir, it was confirmed that the mRNA and protein levels of NF-κB, NLRP3 inflammasome, and inflammatory factors were decreased by the miR-16 by directly targeting TLR4. We also treated A549 cells with miR-16 mimics and anti-miR-16 to confirm the results. Overall, our experiments showed that miR-16 protects against acute lung injury in mice by regulating the TLR4/ NF-κB pathway and attenuating inflammatory response. This work suggests a potential novel therapeutic approach to combat ALI.

Keywords

• Acute lung injury (ALI)
• Mice
• NLRP3 inflammasome
• MicroRNA-16
• TLR4