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

Shi,Ruili; Zhang,Jiancheng; Peng,Zhang; Yuan,Shiying; Gao,Sumin; Chen,Lin; Yuan,Yin

doi:10.3892/ijmm.2018.3443

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

Authors:
- Ruili Shi
- Jiancheng Zhang
- Zhang Peng
- Shiying Yuan
- Sumin Gao
- Lin Chen
- Yin Yuan
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Affiliations: Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: January 30, 2018 https://doi.org/10.3892/ijmm.2018.3443
Pages: 2159-2168

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Abstract

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.

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