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Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells

  • Authors:
    • Yunpeng Luo
    • Wen Che
    • Mingyan Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Intensive Care Unit, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
    Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 297-306
    |
    Published online on: December 13, 2016
       https://doi.org/10.3892/ijmm.2016.2828
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Abstract

Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory properties and has been suggested to modulate lipopolysaccharide (LPS)-induced acute lung injury (ALI). High-mobility group box 1 (HMGB1), a nuclear DNA-binding protein, plays a key role in the development of ALI. The aim of this study was to investigate whether UTI attenuates ALI through the inhibition of HMGB1 expression and to elucidate the underlying molecular mechanisms. ALI was induced in male rats by the intratracheal instillation of LPS (5 mg/kg). UTI was administered intraperitoneally 30 min following exposure to LPS. A549 alveolar epithelial cells were incubated with LPS in the presence or absence of UTI. An enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines. Western blot analysis was performed to detect the changes in the expression levels of Toll-like receptor 2/4 (TLR2/4) and the activation of nuclear factor-κB (NF-κB). The results revealed that UTI significantly protected the animals from LPS-induced ALI, as evidenced by the decrease in the lung wet to dry weight ratio, total cells, neutrophils, macrophages and myeloperoxidase activity, associated with reduced lung histological damage. We also found that UTI post-treatment markedly inhibited the release of HMGB1 and other pro-inflammatory cytokines. Furthermore, UTI significantly inhibited the LPS-induced increase in TLR2/4 protein expression and NF-κB activation in lung tissues. In vitro, UTI markedly inhibited the expression of TLR2/4 and the activation of NF-κB in LPS-stimulated A549 alveolar epithelial cells. The findings of our study indicate that UTI attenuates LPS-induced ALI through the inhibition of HMGB1 expression in rats. These benefits are associated with the inhibition of the activation of the TLR2/4-NF-κB pathway by UTI.
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Copy and paste a formatted citation
Spandidos Publications style
Luo Y, Che W and Zhao M: Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells. Int J Mol Med 39: 297-306, 2017.
APA
Luo, Y., Che, W., & Zhao, M. (2017). Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells. International Journal of Molecular Medicine, 39, 297-306. https://doi.org/10.3892/ijmm.2016.2828
MLA
Luo, Y., Che, W., Zhao, M."Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells". International Journal of Molecular Medicine 39.2 (2017): 297-306.
Chicago
Luo, Y., Che, W., Zhao, M."Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells". International Journal of Molecular Medicine 39, no. 2 (2017): 297-306. https://doi.org/10.3892/ijmm.2016.2828
Copy and paste a formatted citation
x
Spandidos Publications style
Luo Y, Che W and Zhao M: Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells. Int J Mol Med 39: 297-306, 2017.
APA
Luo, Y., Che, W., & Zhao, M. (2017). Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells. International Journal of Molecular Medicine, 39, 297-306. https://doi.org/10.3892/ijmm.2016.2828
MLA
Luo, Y., Che, W., Zhao, M."Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells". International Journal of Molecular Medicine 39.2 (2017): 297-306.
Chicago
Luo, Y., Che, W., Zhao, M."Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells". International Journal of Molecular Medicine 39, no. 2 (2017): 297-306. https://doi.org/10.3892/ijmm.2016.2828
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