Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 37, Issue 1, Pages 99-107Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2015.2410
Keywords
severe acute pancreatitis; high-mobility group box 1; Toll-like receptor 4; nuclear factor-kappa B; recombinant human highmobility; group box 1
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Funding
- National Science Fund for Distinguished Young Scholars [81000186]
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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-kappa B (NF-kappa B) was activated in our mouse model of SAP. We noted that the rhHMGB1 pancreas-targeted injection activated the TLR4-mediated NF-kappa B signaling pathway and induced pancreatic injury in wild-type mice. In TLR4-deficient mice, the rhHMGB1-induced activation of NF-kappa B 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-kappa B signaling pathway is a potential important mediator in the development of this form of pancreatic injury.
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