Open Access

Targeting Notch-activated M1 macrophages attenuate lung tissue damage in a rat model of ventilator induced lung injury

  • Authors:
    • Danping Yin
    • Weiming Wang
    • Wei Han
    • Chen Fan
  • View Affiliations

  • Published online on: August 16, 2019     https://doi.org/10.3892/ijmm.2019.4315
  • Pages: 1388-1398
  • Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ventilator induced lung injury (VILI) may be involved in the activation of alveolar macrophages. The purpose of this study was to investigate the relationship between the Notch signaling pathway and macrophage polarization in VILI. The VILI model was established using rats. Hematoxylin‑eosin staining was used to test the lung tissue morphology. Bicinchoninic acid assay and ELISA were performed to detect protein and tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑10 levels in bronchoalveolar lavage fluids (BALF), respectively. The ratio of alveolar M1 and M2 macrophages was detected by flow cytometry. The mRNA and protein expression levels of Notch pathway‑related proteins were determined using reverse transcription‑quantitative PCR and western blotting. The present study found that high‑frequency mechanical ventilation could cause pulmonary edema and increase the levels of protein, TNF‑α and IL‑6 in BALF while decreasing the level of IL‑10 in BALF. High‑frequency mechanical ventilation also induced polarization of alveolar macrophages to M1. The results also showed a significant increase in the levels of Notch pathway‑related proteins including notch intracellular domain, Hes1, Hes5 and Hey1. Injection of N‑[N‑(3,5‑difluorophenylacetyl)‑1‑alanyl] phenylglycine t‑butyl ester could inhibit the Notch pathway and such an inhibition protected lung tissue and reduced lung inflammation caused by mechanical ventilation. After the Notch pathway was inhibited, the level of M1 polarization of macrophages caused by high‑frequency mechanical ventilation was reduced. VILI caused pulmonary inflammation and macrophages to polarize to M1 and upregulated the expression levels of Notch pathway‑related proteins. The inhibition of Notch pathway also reduced the proportion of M1 macrophages and inflammatory responses.

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October 2019
Volume 44 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
APA
Yin, D., Wang, W., Han, W., & Fan, C. (2019). Targeting Notch-activated M1 macrophages attenuate lung tissue damage in a rat model of ventilator induced lung injury. International Journal of Molecular Medicine, 44, 1388-1398. https://doi.org/10.3892/ijmm.2019.4315
MLA
Yin, D., Wang, W., Han, W., Fan, C."Targeting Notch-activated M1 macrophages attenuate lung tissue damage in a rat model of ventilator induced lung injury". International Journal of Molecular Medicine 44.4 (2019): 1388-1398.
Chicago
Yin, D., Wang, W., Han, W., Fan, C."Targeting Notch-activated M1 macrophages attenuate lung tissue damage in a rat model of ventilator induced lung injury". International Journal of Molecular Medicine 44, no. 4 (2019): 1388-1398. https://doi.org/10.3892/ijmm.2019.4315