E3 Ubiquitin Ligase TRIM7 Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting NLRP3 Inflammasome Activation

Abstract

Acute lung injury (ALI) is a common clinical disease with high mortality, characterized by tissue damage caused by excessive activation of inflammation. TRIM7 is an E3 ligase that plays an important role in regulating viral infection, tumor progression, and innate immune response. However, its function in ALI is unclear. In this study, lipopolysaccharide (LPS) was used to stimulate C57BL/6j mice and HULEC-5a cells to establish ALI models in vivo and in vitro. TRIM7 expression was down-regulated during ALI. Furthermore, overexpressing TRIM7 in HULEC-5a cells relieved cell damage and inflammatory activation induced by LPS stimulation. TRIM7 knockdown had the opposite effect. Trim7-overexpressing mice were established by endotracheal injection of adeno-associated virus 6-Trim7 virus in vivo; the ALI model was then induced by LPS stimulation. Overexpression of TRIM7 could alleviate lung tissue injury, pulmonary interstitial hemorrhage, increased alveolar and vascular permeability, inflammatory cell infiltration, and secretion of inflammatory factors induced by LPS stimulation. Mechanistically, TRIM7 inhibited the expression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3) and the activation of the NLRP3 inflammasome. The regulatory effect of TRIM7 on ALI depended on the NLRP3 inflammasome. This investigation, for the first time, showed the inhibitory effect of TRIM7 on ALI and activation of the NLRP3 inflammasome, providing new targets and ideas for the research on the mechanism and treatment of ALI.