LAUSR

Endothelial cell (EC) inflammation is regarded as an important pathogenic feature of many inflammatory diseases such as acute lung injury and sepsis. Increase in EC inflammation results in neutrophil infiltration from the blood to the site of inflammation, further promoting EC permeability. Ubiquitin E3 ligase TRIM21 has been known to be implicated in human disorders; however, the roles of TRIM21 in endothelial dysfunction and acute lung injury have not been reported. Here we reveal an anti-inflammatory property of TRIM21 in a mouse model of acute lung injury and human lung microvascular endothelial cells (HLMVECs). Overexpression of TRIM21 by lentiviral vector infection effectively dampened lipopolysaccharide (LPS)-induced neutrophil infiltration, cytokine release, and edema in mice. TRIM21 inhibits HLMVECs inflammatory responses evidenced by attenuation of NF-κB pathway, IL-8 release, intercellular adhesion molecules expression, and monocytes adhesion to ECs. Furthermore, we demonstrated that TRIM21 was predominantly degraded through increasing its mono-ubiquitination and lysosomal degradation after inflammatory stimuli. Thus, inhibition of vascular endothelial inflammation by TRIM21 provides a novel therapeutic target to lessen pulmonary inflammation.