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JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling

  • Authors:
    • Jingxian Du
    • Gaojian Wang
    • Huanyu Luo
    • Na Liu
    • Junran Xie
  • View Affiliations / Copyright

    Affiliations: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310020, P.R. China
    Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 150
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    Published online on: December 20, 2020
       https://doi.org/10.3892/mmr.2020.11789
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Abstract

JNK serves critical roles in numerous types of inflammation‑ and oxidative stress‑induced disease, including acute lung injury (ALI). JNK‑IN‑8 is the first irreversible JNK inhibitor that has been described. However, whether JNK‑IN‑8 can prevent lipopolysaccharide (LPS)‑induced ALI by inhibiting JNK activation and its downstream signaling is poorly understood. The objective of the present study was to investigate the specific therapeutic effects of JNK‑IN‑8 on LPS‑induced ALI and the molecular mechanisms involved. JNK‑IN‑8 attenuated myeloperoxidase activity, malondialdehyde and superoxide dismutase content and the lung wet/dry ratio, and improved the survival rate following lethal injection of LPS. Additionally, JNK‑IN‑8 decreased bronchoalveolar lavage fluid protein levels, lactate dehydrogenase activity, neutrophil infiltration and the number of macrophages (as demonstrated by flow cytometry), as well as the production of TNF‑α, IL‑6 and IL‑1β (as evaluated via ELISA). In addition, reverse transcription‑quantitative PCR and ELISA showed that JNK‑IN‑8 attenuated LPS‑induced inflammatory cytokine production and oxidative stress in primary murine peritoneal macrophages and RAW264.7 cells in vitro. Furthermore, the present study demonstrated that the JNK/NF‑κB signaling pathway was involved in the therapeutic effect of JNK‑IN‑8 against LPS‑induced injury both in vivo and in vitro. In conclusion, these findings indicated that JNK‑IN‑8 had a therapeutic effect on LPS‑induced ALI in mice. The mechanism may be associated with inhibition of the JNK/NF‑κB signaling pathway. JNK‑IN‑8 may be a potential therapeutic agent for the treatment of ALI.
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Copy and paste a formatted citation
Spandidos Publications style
Du J, Wang G, Luo H, Liu N and Xie J: JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling. Mol Med Rep 23: 150, 2021.
APA
Du, J., Wang, G., Luo, H., Liu, N., & Xie, J. (2021). JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling. Molecular Medicine Reports, 23, 150. https://doi.org/10.3892/mmr.2020.11789
MLA
Du, J., Wang, G., Luo, H., Liu, N., Xie, J."JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling". Molecular Medicine Reports 23.2 (2021): 150.
Chicago
Du, J., Wang, G., Luo, H., Liu, N., Xie, J."JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling". Molecular Medicine Reports 23, no. 2 (2021): 150. https://doi.org/10.3892/mmr.2020.11789
Copy and paste a formatted citation
x
Spandidos Publications style
Du J, Wang G, Luo H, Liu N and Xie J: JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling. Mol Med Rep 23: 150, 2021.
APA
Du, J., Wang, G., Luo, H., Liu, N., & Xie, J. (2021). JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling. Molecular Medicine Reports, 23, 150. https://doi.org/10.3892/mmr.2020.11789
MLA
Du, J., Wang, G., Luo, H., Liu, N., Xie, J."JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling". Molecular Medicine Reports 23.2 (2021): 150.
Chicago
Du, J., Wang, G., Luo, H., Liu, N., Xie, J."JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling". Molecular Medicine Reports 23, no. 2 (2021): 150. https://doi.org/10.3892/mmr.2020.11789
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