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Article

Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis

  • Authors:
    • Jing Wang
    • Chun Zhang
    • Ping Xu
    • Zhi‑Wen Yang
    • Cheng‑Zhao Weng
    • Yue‑Xing Lai
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Shanghai Songjiang Hospital Affiliated to Nanjing Medical University, Shanghai 201600, P.R. China, Department of Pharmacy, Songjiang Hospital Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 201600, P.R. China, Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200030, P.R. China
  • Pages: 7835-7844
    |
    Published online on: March 29, 2018
       https://doi.org/10.3892/mmr.2018.8819
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Abstract

Phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) has been indicated to serve an important role in the pathogenesis of inflammatory diseases. It was previously demonstrated that the PI3K/Akt inhibitor wortmannin alleviated the severity of inflammation and improved the survival rate in rats with induced severe acute pancreatitis (SAP), which indicates that PI3K/Akt may serve a role in the pathogenesis of acute pancreatitis. To date, the mechanism by which PI3K/Akt regulates inflammation has not been elucidated. In the present study, it was hypothesized that PI3K/Akt may be invovled in SAP inflammation via regulation of the Toll‑like receptor 4 (TLR4) signaling pathway. Rats with SAP were treated with the PI3K/Akt agonist insulin‑like growth factor (IGF)‑1, which alleviated the severity of inflammation in a dose‑dependent manner. Furthermore, to better understand the role of PI3K/Akt in inflammation, RAW264.7 murine macrophages were stimulated with IGF‑1 and wortmannin alone or together before the induction of inflammation by treatment with lipopolysaccharide (LPS). The results indicated that LPS stimulated overexpression of TLR4, myeloid differentiation primary response gene 88 (MyD88), PI3K, Akt, p38MAPK and NF‑κBp65 mRNA, and increased the levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 in RAW264.7 cells compared with the control group. The levels of all detected factors were increased by stimulation with IGF‑1, whereas these levels were decreased following treatment with wortmannin alone, and the effect of IGF‑1 was abolished by wortmannin in RAW264.7 cells. In vivo studies indicated that IGF‑1 produced the same anti‑inflammatory effect as wortmannin and that expression of TLR4, p38MAPK and NF‑κBp65 decreased following treatment with IGF‑1. These findings indicate that PI3K/Akt may take part in the progression of SAP by regulating the TLR4 signaling pathway and that IGF‑1 can inhibit inflammation in SAP rats.
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Copy and paste a formatted citation
Spandidos Publications style
Wang J, Zhang C, Xu P, Yang ZW, Weng CZ and Lai YX: Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis. Mol Med Rep 17: 7835-7844, 2018.
APA
Wang, J., Zhang, C., Xu, P., Yang, Z., Weng, C., & Lai, Y. (2018). Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis. Molecular Medicine Reports, 17, 7835-7844. https://doi.org/10.3892/mmr.2018.8819
MLA
Wang, J., Zhang, C., Xu, P., Yang, Z., Weng, C., Lai, Y."Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis". Molecular Medicine Reports 17.6 (2018): 7835-7844.
Chicago
Wang, J., Zhang, C., Xu, P., Yang, Z., Weng, C., Lai, Y."Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis". Molecular Medicine Reports 17, no. 6 (2018): 7835-7844. https://doi.org/10.3892/mmr.2018.8819
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Zhang C, Xu P, Yang ZW, Weng CZ and Lai YX: Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis. Mol Med Rep 17: 7835-7844, 2018.
APA
Wang, J., Zhang, C., Xu, P., Yang, Z., Weng, C., & Lai, Y. (2018). Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis. Molecular Medicine Reports, 17, 7835-7844. https://doi.org/10.3892/mmr.2018.8819
MLA
Wang, J., Zhang, C., Xu, P., Yang, Z., Weng, C., Lai, Y."Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis". Molecular Medicine Reports 17.6 (2018): 7835-7844.
Chicago
Wang, J., Zhang, C., Xu, P., Yang, Z., Weng, C., Lai, Y."Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis". Molecular Medicine Reports 17, no. 6 (2018): 7835-7844. https://doi.org/10.3892/mmr.2018.8819
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