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Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils

  • Authors:
    • Chen Bai
    • Zhengchen Jiang
    • Hongxin Jiang
    • Shuna Yu
    • Ming Li
    • Fangfang Chu
    • Yaxin Sheng
    • Jianguo Li
    • Jiying Jiang
    • Wanzhen Li
  • View Affiliations / Copyright

    Affiliations: Department of Anatomy, Basic Medical College of Weifang Medical University, Weifang, Shandong 261053, P.R. China, General Surgery Department, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250013, P.R. China, Morphology Laboratory, Basic Medical College of Weifang Medical University, Weifang, Shandong 261053, P.R. China
    Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 673
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    Published online on: September 14, 2022
       https://doi.org/10.3892/etm.2022.11609
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Abstract

Inflammation is one of the most crucial mechanism underlying hepatic ischemia‑reperfusion injury (HIRI). Several studies have shown that Ac2‑26, the active N‑terminal peptide of Annexin A1, could modulate anti‑inflammatory processes and protect the organs from ischemia‑reperfusion injury (IRI). However the effects of Ac2‑26 on an HIRI model have not been reported to date. The purpose of the present study was to determine whether Ac2‑26 pretreatment could protect hepatocytes against acute HIRI by inhibiting neutrophil infiltration through regulation of the high mobility group box protein 1 (HMGB1)/Toll‑like receptor 4 (TLR4)/NF‑κB signaling pathway. To this end, a total of 72 adult C57BL/6 mice were randomly divided into sham operation (sham), ischemia‑reperfusion (I/R), I/R + Ac2‑26 and Ac2‑26 groups. The HIRI model was established by occluding the branch of the hepatic pedicle to the left and median liver lobes with an atraumatic vascular clamp for 45 min, followed by reperfusion for 24 h. The expression of HMGB1, TLR4, NF‑κB, IκBα and lymphocyte antigen 6 complex locus G6D (Ly6G) was detected using reverse transcription‑quantitative PCR, western blotting and immunohistochemical staining; serum levels of HMGB1 were evaluated using an enzyme‑linked immunosorbent assay. Flow cytometry was used to detect the proportion of neutrophil. The results indicated that Ac2‑26 preconditioning rescued hepatocyte dysfunctions induced by HIRI. In addition, HIRI was associated with a significant increase in HMGB1 expression and release, accompanied by increased expression of TLR4, which was significantly inhibited by Ac2‑26. Furthermore, the expression of phosphorylated (p)‑NF‑κB and the ratio of p‑NF‑κB to NF‑κB were markedly increased, while the expression of IκBα was decreased in the I/R group compared with those in the sham group; however, these effects were reversed by Ac2‑26 administration. Additionally, Ac2‑26 administration significantly inhibited neutrophil infiltration and resulted in low levels of neutrophils and Ly6G as well as reduced myeloperoxidase activity. Taken together, these results indicated that Ac2‑26 pretreatment serves a protective role against HIRI by regulating the HMGB1/TLR4/NF‑κB signaling pathway and inhibiting neutrophil infiltration.
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Copy and paste a formatted citation
Spandidos Publications style
Bai C, Jiang Z, Jiang H, Yu S, Li M, Chu F, Sheng Y, Li J, Jiang J, Li W, Li W, et al: Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils. Exp Ther Med 24: 673, 2022.
APA
Bai, C., Jiang, Z., Jiang, H., Yu, S., Li, M., Chu, F. ... Li, W. (2022). Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils. Experimental and Therapeutic Medicine, 24, 673. https://doi.org/10.3892/etm.2022.11609
MLA
Bai, C., Jiang, Z., Jiang, H., Yu, S., Li, M., Chu, F., Sheng, Y., Li, J., Jiang, J., Li, W."Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils". Experimental and Therapeutic Medicine 24.5 (2022): 673.
Chicago
Bai, C., Jiang, Z., Jiang, H., Yu, S., Li, M., Chu, F., Sheng, Y., Li, J., Jiang, J., Li, W."Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils". Experimental and Therapeutic Medicine 24, no. 5 (2022): 673. https://doi.org/10.3892/etm.2022.11609
Copy and paste a formatted citation
x
Spandidos Publications style
Bai C, Jiang Z, Jiang H, Yu S, Li M, Chu F, Sheng Y, Li J, Jiang J, Li W, Li W, et al: Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils. Exp Ther Med 24: 673, 2022.
APA
Bai, C., Jiang, Z., Jiang, H., Yu, S., Li, M., Chu, F. ... Li, W. (2022). Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils. Experimental and Therapeutic Medicine, 24, 673. https://doi.org/10.3892/etm.2022.11609
MLA
Bai, C., Jiang, Z., Jiang, H., Yu, S., Li, M., Chu, F., Sheng, Y., Li, J., Jiang, J., Li, W."Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils". Experimental and Therapeutic Medicine 24.5 (2022): 673.
Chicago
Bai, C., Jiang, Z., Jiang, H., Yu, S., Li, M., Chu, F., Sheng, Y., Li, J., Jiang, J., Li, W."Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils". Experimental and Therapeutic Medicine 24, no. 5 (2022): 673. https://doi.org/10.3892/etm.2022.11609
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