Abstract

BACKGROUND: Acute lung injury (ALI) often occurs early and seriously in the progress of sepsis. Netrin-1 is demonstrated to be an effective anti-inflammatory agent. However, whether netrin-1 can relieve sepsis-induced ALI remains unknown.

MATERIAL AND METHODS: The sepsis rat model was built with the method of cecal ligation and puncture (CLP). The lung tissue changes were represented as the results of hematoxylin-eosin (HE) staining, wet-to-dry (W/D) ratio, Western blot analysis, and immunohistochemistry. An in vitro lung injury model was simulated with LPS-induced BEAS-2B cells. The cell transfection effects were evaluated by Western blot analysis and RT-qPCR analysis. TNF-α, IL-1β, and IL-6 levels were detected by Western blot analysis in LPS-induced BEAS-2B cells.

RESULTS: Obvious inflammation caused by sepsis appeared in lung tissues with the increase of the W/D ratio and expression of inflammatory cytokines. Netrin-1 and its receptor UNC5B were reduced in sepsis. However, upregulation of netrin-1 alleviated the levels of inflammation and increased the UNC5B levels in BEAS-2B cells.

CONCLUSIONS: Netrin-1 protects against ALI in sepsis rats through its anti-inflammation effect and may provide a novel treatment to prevent lung injury caused by sepsis.

Keywords: acute lung injury, exosomes, Sepsis, Anti-Inflammatory Agents, Bronchoalveolar Lavage Fluid, Cytokines, Lung, Netrin-1