Expression level of 12-amino acid triggering receptor on myeloid cells-like transcript 1 derived peptide alleviates lipopolysaccharide-induced acute lung injury in mice

摘要

Acute lung injury (ALI) is a critical illness with a high morbidity and mortality rate due to severe inflammation in the lungs. The effects and underlying mechanism of the triggering receptor expressed on myeloid cells-1 (TREM-1)-like transcript-1-derived peptide (LR12) on ALI remain unclear. The aim of the present study was to determine whether LR12 attenuates lipopolysaccharide (LPS)-induced ALI and elucidate the mechanism underlying it. Male C57BL/6 mice were randomly assigned to three groups as follows: Sham group, LPS + scramble group and LPS + LR12 group. Normal saline (NS) or LPS was administrated by intratracheal instillation, and NS, LR12 or LR12 scramble was administered intraperitoneally 30 min later. The treatment was repeated every 3 h three times. Mice were sacrificed 24 h later. Pulmonary pathological changes, the lung wet/dry weight ratio, the macrophage and neutrophil counts in bronchoalveolar lavage fluid and myeloperoxidase (MPO) activity in the lung tissues were observed. The inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay and lung neutrophil infiltration was detected by immunohistochemistry. Nuclear factor (NF)-B p65 and TREM-1 were analyzed by western blotting, and the activation of NF-B was detected by electrophoretic mobility shift assay. LPS-induced pathohistological injury, edema and neutrophil infiltration were significantly alleviated by TREM-1 inhibitor, LR12. The proinflammatory cytokines [interleukin (IL)-6, IL-1, tumor necrosis factor-] and chemokines (keratinocyte chemokine and monocyte chemoattractant protein-1) were significantly reduced, whereas the anti-inflammatory cytokines, IL-10 were significantly increased by LR12. LR12 was identified to significantly decrease p65 expression levels in the nucleus and inhibit the activity of NF-B. Furthermore, LR12 alleviated LPS-induced ALI by reducing the expression of TREM-1, increasing the release of soluble TREM-1 and inhibiting activation of the NF-B signaling pathway.