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)‑κB p65 and TREM‑1 were analyzed by western blotting, and the activation of NF‑κB 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‑1β,
tumor necrosis factor‑α] 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‑κB. 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-κB signaling pathway.