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Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction

  • Authors:
    • Chao Chang
    • Liya Hu
    • Shanshan Sun
    • Yanqiu Song
    • Shan Liu
    • Jing Wang
    • Peijun Li
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Surgical ICU, Tianjin Chest Hospital, Nankai University, Tianjin 300222, P.R. China, Department of Critical Care Medicine, The Third Central Hospital of Tianjin, Tianjin 300170, P.R. China, Department of Emergency, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Tianjin Cardiovascular Institute, Tianjin Chest Hospital, Tianjin 300222, P.R. China, Department of Pathology, Tianjin Chest Hospital, Nankai University, Tianjin 300222, P.R. China
    Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 334
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    Published online on: March 8, 2021
       https://doi.org/10.3892/mmr.2021.11973
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Abstract

Sepsis is a life‑threatening organ dysfunction caused by a dysregulated host response to infection, and is a leading cause of mortality worldwide. Myocardial dysfunction is associated with poor prognosis in patients with sepsis and contributes to a high risk of mortality. However, the pathophysiological mechanisms underlying sepsis‑induced myocardial dysfunction are not completely understood. The aim of the present study was to investigate the role of toll‑like receptor 4 (TLR4)/c‑Jun N‑terminal kinase (JNK) signaling in pro‑inflammatory cytokine expression and cardiac dysfunction during lipopolysaccharide (LPS)‑induced sepsis in mice. C57BL/6 mice were pretreated with TAK‑242 or saline for 1 h and then subjected to LPS (12 mg/kg, intraperitoneal) treatment. Cardiac function was assessed using an echocardiogram. The morphological changes of the myocardium were examined by hematoxylin and eosin staining and transmission electron microscopy. The serum protein levels of cardiac troponin I (cTnI) and tumor necrosis factor‑α (TNF‑α) were determined by an enzyme‑linked immunosorbent assay (ELISA). The TLR4 and JNK mRNA levels were analyzed via reverse transcription‑quantitative PCR. TLR4, JNK and phosphorylated‑JNK protein levels were measured by western blotting. In response to LPS, the activation of TLR4 and JNK in the myocardium was upregulated. There were significant increases in the serum levels of TNF‑α and cTnI, as well as histopathological changes in the myocardium and suppressed cardiac function, following LPS stimulation. Inhibition of TLR4 activation using TAK‑242 led to a decrease in the activation of JNK and reduced the protein expression of TNF‑α in plasma, and alleviated histological myocardial injury and improved cardiac function during sepsis in mice. The present data suggested that the TLR4/JNK signaling pathway played a critical role in regulating the production of pro‑inflammatory cytokines and myocardial dysfunction induced by LPS.
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Copy and paste a formatted citation
Spandidos Publications style
Chang C, Hu L, Sun S, Song Y, Liu S, Wang J and Li P: Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction. Mol Med Rep 23: 334, 2021.
APA
Chang, C., Hu, L., Sun, S., Song, Y., Liu, S., Wang, J., & Li, P. (2021). Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction. Molecular Medicine Reports, 23, 334. https://doi.org/10.3892/mmr.2021.11973
MLA
Chang, C., Hu, L., Sun, S., Song, Y., Liu, S., Wang, J., Li, P."Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction". Molecular Medicine Reports 23.5 (2021): 334.
Chicago
Chang, C., Hu, L., Sun, S., Song, Y., Liu, S., Wang, J., Li, P."Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction". Molecular Medicine Reports 23, no. 5 (2021): 334. https://doi.org/10.3892/mmr.2021.11973
Copy and paste a formatted citation
x
Spandidos Publications style
Chang C, Hu L, Sun S, Song Y, Liu S, Wang J and Li P: Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction. Mol Med Rep 23: 334, 2021.
APA
Chang, C., Hu, L., Sun, S., Song, Y., Liu, S., Wang, J., & Li, P. (2021). Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction. Molecular Medicine Reports, 23, 334. https://doi.org/10.3892/mmr.2021.11973
MLA
Chang, C., Hu, L., Sun, S., Song, Y., Liu, S., Wang, J., Li, P."Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction". Molecular Medicine Reports 23.5 (2021): 334.
Chicago
Chang, C., Hu, L., Sun, S., Song, Y., Liu, S., Wang, J., Li, P."Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction". Molecular Medicine Reports 23, no. 5 (2021): 334. https://doi.org/10.3892/mmr.2021.11973
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