Open Access

Necrostatin‑1 protects mice from acute lung injury by suppressing necroptosis and reactive oxygen species

  • Authors:
    • Bi Lin
    • Ziyuan Jin
    • Xiang Chen
    • Li Zhao
    • Chengwei Weng
    • Baihui Chen
    • Yaning Tang
    • Lina Lin
  • View Affiliations

  • Published online on: March 3, 2020     https://doi.org/10.3892/mmr.2020.11010
  • Pages: 2171-2181
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI) is characterized by tissue damage and inflammatory cytokine secretion; however, the therapeutic options available to treat ALI remain limited. Necrostatin‑1 (Nec‑1) has the ability to attenuate cell necroptosis in various inflammatory diseases. The present study evaluated the protective effects of Nec‑1 on a mouse model of lipopolysaccharide‑induced ALI. Histological alterations in the lungs were evaluated through hematoxylin and eosin staining, and the expression levels of cytokines in the bronchoalveolar lavage fluid and lung tissues were determined by ELISA. In addition, accumulated production of reactive oxygen species was determined by staining with DCFH‑DA probes, western blotting and immunofluorescence. The results revealed that treatment with the necroptosis inhibitor, Nec‑1, exerted significant protective effects on ALI‑induced inflammation and necroptosis. The key proteins involved in necroptosis were markedly reduced, including receptor‑interacting serine/threonine‑protein kinase (RIP)1 and RIP3. Notably, antioxidant proteins were upregulated by Nec‑1, which may attenuate oxidative stress. Furthermore, treatment with Nec‑1 markedly suppressed necroptosis in the pulmonary alveoli RLE‑6TN cell line. Taken together, these data revealed a novel association between ALI and necroptosis, and suggested that necroptosis inhibitors may be used as effective anti‑inflammatory drugs to treat ALI.

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May 2020
Volume 21 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Lin, B., Jin, Z., Chen, X., Zhao, L., Weng, C., Chen, B. ... Lin, L. (2020). Necrostatin‑1 protects mice from acute lung injury by suppressing necroptosis and reactive oxygen species. Molecular Medicine Reports, 21, 2171-2181. https://doi.org/10.3892/mmr.2020.11010
MLA
Lin, B., Jin, Z., Chen, X., Zhao, L., Weng, C., Chen, B., Tang, Y., Lin, L."Necrostatin‑1 protects mice from acute lung injury by suppressing necroptosis and reactive oxygen species". Molecular Medicine Reports 21.5 (2020): 2171-2181.
Chicago
Lin, B., Jin, Z., Chen, X., Zhao, L., Weng, C., Chen, B., Tang, Y., Lin, L."Necrostatin‑1 protects mice from acute lung injury by suppressing necroptosis and reactive oxygen species". Molecular Medicine Reports 21, no. 5 (2020): 2171-2181. https://doi.org/10.3892/mmr.2020.11010