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

Abstract

Acute lung injury (ALI) is a clinically common 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. Its function in ALI is unclear, however. 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. The results showed that 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 has 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. We showed that 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 has been shown to inhibit the expression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3) and activation of the NLRP3 inflammasome. The regulatory effect of TRIM7 on ALI depends on the NLRP3 inflammasome. This investigation for the first time shows the inhibitory effect of TRIM7 on ALI and activation of the NLRP3 inflammasome, providing new targets and ideas for the mechanism research and treatment of ALI.