Surgery Today

, Volume 37, Issue 10, pp 867–873

Role of Toll-Like Receptor 4 in the Pathophysiology of Severe Acute Pancreatitis in Mice

  • Hidehiro Sawa
  • Takashi Ueda
  • Yoshifumi Takeyama
  • Takeo Yasuda
  • Makoto Shinzeki
  • Takahiro Nakajima
  • Yoshikazu Kuroda
Original Article

DOI: 10.1007/s00595-007-3520-x

Cite this article as:
Sawa, H., Ueda, T., Takeyama, Y. et al. Surg Today (2007) 37: 867. doi:10.1007/s00595-007-3520-x

Abstract

Purpose

Multiple organ dysfunction and infection are major contributors to the high mortality associated with severe acute pancreatitis (SAP). Toll-like receptor 4 (TLR4) recognizes the lipopolysaccharide of gram-negative bacilli and is involved in inflammatory response and host defense. We examined the effects of TLR4-deficiency in SAP in mice.

Methods

Closed duodenal loop-induced pancreatitis was induced in C3H/HeN (wild-type) and C3H/HeJ (TLR4-deficient) mice. We compared the severity of pancreatitis, liver and kidney dysfunction, and bacterial translocation to the pancreas between the two types of mice 12 h after the induction of SAP.

Results

The severity of pancreatitis was similar in the two types of mice. The TLR4-deficient mice had significantly lower serum levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine; significantly lower serum levels of interleukin-1 and tumor necrosis factor; reduced apoptosis of the liver and kidney; and a significantly higher rate of positive gram-negative bacterial cultures of the pancreas. TLR4 protein expression in the liver, kidney, and small intestine was increased 4 h after the induction of SAP, and decreased 12 h after the induction of SAP.

Conclusions

TLR4 is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP, and TLR4 may trigger the inflammatory response and function defensively against infection.

Key words

Severe acute pancreatitis TLR4-deficiency C3H/HeJ mice Organ dysfunction Bacterial translocation 

Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Hidehiro Sawa
    • 1
  • Takashi Ueda
    • 1
  • Yoshifumi Takeyama
    • 2
  • Takeo Yasuda
    • 1
  • Makoto Shinzeki
    • 1
  • Takahiro Nakajima
    • 1
  • Yoshikazu Kuroda
    • 1
  1. 1.Department of Gastroenterological SurgeryKobe University Graduate School of Medical SciencesKobeJapan
  2. 2.Department of SurgeryKinki University School of MedicineOsaka-SayamaJapan

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