BAP31 regulates the expression of ICAM-1/VCAM-1 via MyD88/NF-κB pathway in acute lung injury mice model

Aims: The cell adhesion molecules (CAMs) that mediate neutrophil-endothelium cell adhesion are deeply involved in the pathogenesis of acute lung injury (ALI). B-cell receptor associated protein 31 (BAP31) has been reported to engage in the expression of some CAMs. This study was undertaken to explore whether BAP31 in endotheliocyte affects the pathological process of ALI by regulating CAMs, and its possible mechanism.

Main methods: Our study used the shBAP31 endothelium cell lines and endothelial-specific BAP31 conditional knockdown mice constructed via Cre/loxP system. Hematoxylin and eosin staining was used to observe the histopathological manifestations. The adhesion of neutrophils to vascular wall was examined by intravital microscopy. The nuclear translocation of NF-κB was observed by immunofluorescence staining assay. Flow cytometric, real-time polymerase chain reaction and Western blot assay were performed to determine the expression of CAMs and key proteins in MyD88/NF-κB-related signaling pathway. Luciferase reporter and chromatin immunoprecipitation assay were analyzed for transcriptional activity of ICAM-1 and VCAM-1.

Key findings: Mechanistic investigations indicated that endothelium-specific BAP31 depletion dramatically reduced the capacity of neutrophils adherence to endothelial cells (ECs), which was mainly attributed to the significant downregulation of ICAM-1 (p < 0.05) and VCAM-1 (p < 0.05) expression. Interestingly, BAP31 knockdown apparently deactivated MyD88/TRAF6-mediated TAK1/NF-κB and PI3K/Akt signaling cascades, resulting in the inhibition of NF-κB activation and nuclear translocation.

Significance: Our data furnished convincing evidence that BAP31 deficiency performs a mitigative effect on ALI by decreasing neutrophils-ECs adhesion. These findings identified BAP31 as a promising protein for regulating the pathogenesis process of ALI.