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objectivesTo investigate the protective effect of lipocalin-2 (LCN2) gene knockout against sepsis-induced acute lung injury (ALI) and vascular endothelial dysfunction in mice and the mediating role of the nuclear factor-κB (NF-κB) signaling pathway.

methodsWild-type (WT) C57BL/6 mice receiving sham operation or cecal ligation and puncture (CLP) to induce sepsis were randomized into 3 subgroups for intraperitoneal injections of saline, PDTC, or Bay 11-7082 (

resultsThe WT mice receiving CLP showed severe lung structural damage with obvious edema and inflammation. In contrast, both the LCN2KO mouse and PDTC-treated WT mouse models of CLP showed milder lung injury with lower W/D ratio, lung index, Evans blue leakage, serum TNF‑α and IL-6 levels and markedly reduced colocalization signals of NF-κB, ICAM-1, and VCAM-1 with CD31. CLP resulted in significantly increased expression levels of LCN2, p-P65/P65, ICAM-1, and VCAM-1, lowered VE-cadherin levels, and enhanced endothelial cell apoptosis, and all these changes were significantly ameliorated in LCN2KO mice and WT mice with NF‑κB inhibitor treatment. Co-immunoprecipitation results suggested the interaction between lung LCN2 and P65. Bay 11-7082 significantly reduced inflammatory cytokine production, downregulated p-P65 expression and its downstream adhesion molecules, and restored VE-cadherin expression.

conclusionsLCN2 knockout alleviates sepsis-induced ALI and vascular endothelial dysfunction in mice by inhibiting NF-κB signaling.