Open Access

TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis

  • Authors:
    • Gang Li
    • Xuejun Wu
    • Le Yang
    • Yuxiang He
    • Yang Liu
    • Xing Jin
    • Hai Yuan
  • View Affiliations

  • Published online on: November 13, 2015     https://doi.org/10.3892/ijmm.2015.2410
  • Pages: 99-107
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Severe acute pancreatitis (SAP) is an extremely dangerous acute abdominal disorder which causes multiple complications and has a high mortality rate. Previous research has suggested that high-mobility group box 1 (HMGB1) plays an important role in the pathogenesis of SAP; however, the mechanisms underlying this strong correlation remain unclear. In this study, to further investigate whether HMGB1 acts as a stimulating factor, and whether Toll-like receptor 4 (TLR4) acts as its major mediator in the development of pancreatic injury during SAP, recombinant human HMGB1 (rhHMGB1) and TLR4-deficient mice were used. We found that HMGB1 and TLR4 were highly expressed, and nuclear factor-κB (NF-κB) was activated in our mouse model of SAP. We noted that the rhHMGB1 pancreas-targeted injection activated the TLR4-mediated NF-κB signaling pathway and induced pancreatic injury in wild-type mice. In TLR4-deficient mice, the rhHMGB1-induced activation of NF-κB and pathological changes in the pancreas were less evident than in wild-type mice. Therefore, this study provides evidence that HMGB1 promotes the pathogenesis of pancreatitis, and its downstream TLR4-mediated NF-κB signaling pathway is a potential important mediator in the development of this form of pancreatic injury.
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January-2016
Volume 37 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li G, Wu X, Yang L, He Y, Liu Y, Jin X and Yuan H: TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis. Int J Mol Med 37: 99-107, 2016
APA
Li, G., Wu, X., Yang, L., He, Y., Liu, Y., Jin, X., & Yuan, H. (2016). TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis. International Journal of Molecular Medicine, 37, 99-107. https://doi.org/10.3892/ijmm.2015.2410
MLA
Li, G., Wu, X., Yang, L., He, Y., Liu, Y., Jin, X., Yuan, H."TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis". International Journal of Molecular Medicine 37.1 (2016): 99-107.
Chicago
Li, G., Wu, X., Yang, L., He, Y., Liu, Y., Jin, X., Yuan, H."TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis". International Journal of Molecular Medicine 37, no. 1 (2016): 99-107. https://doi.org/10.3892/ijmm.2015.2410