Role of nitric oxide in Toll-like receptor 2 and 4 mRNA expression in liver of acute hemorrhagic necrotizing pancreatitis rats

World J Gastroenterol. 2006 Jan 21;12(3):485-8. doi: 10.3748/wjg.v12.i3.485.

Abstract

Aim: To investigate the role of nitric oxide (NO) in Toll-like receptor 2 (TLR2)/4mRNA expression in livers of acute hemorrhagic necrotizing pancreatitis (AHNP) rats.

Methods: One hundred and ten SD male rats were randomly divided into sham-operated group (n=10), AHNP group (n=30), chloroquine (CQ)-treated group (n=30) and L-Arg-treated group (n=40). TLR2/4mRNA expression in the liver of AHNP rats was measured by RT-PCR.

Results: Expression of TLR2/4mRNA could be detected in the liver of AHNP rats in sham-operated group (0.155E-5+/-0.230E-6 and 0.115E-2+/-0.545E-4), but was markedly increased at 3 h in AHNP group (0.197E-2+/-0.114E-3 and 0.175+/-0.349E-2) peaking at 12 h (0.294E-2+/-0.998E-4 and 2.673+/-2.795E-2, P<0.01). Hepatic injuries were aggravated, TNF-alpha concentration in the liver was increased and NO concentration was decreased (P<0.05 or P<0.01). When TLR2/4mRNA expression was inhibited by CQ (3 h: 1.037E-4+/-3.299E-6 and 0.026+/-3.462E-3; 6 h: 1.884E-4+/-4.679E-6 and 0.108+/-6.115E-3; 12 h: 2.443E-4+/-7.714E-6 and 0.348+/-6.807E-3; P<0.01), hepatic injuries were relieved, NO concentration in the liver was increased and TNF-alpha concentration was decreased (P<0.05 or P<0.01). When rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the liver could be effectively inhibited (50 mg-T: 0.232E-2+/-0.532E-4 and 0.230+/-6.883E-3; 100 mg-T: 0.210E-2+/-1.691E-4 and 0.187+/-0.849E-2; 200 mg-T: 0.163E-2+/-0.404E-4 and 0.107+/-0.195E-2; 400 mg-T: 0.100E-2+/-0.317E-4 and 0.084+/-0.552E-2; P<0.01) and hepatic injuries were relieved. At the same time, NO concentration in the liver was markedly increased and TNF-alpha concentration was decreased (P<0.05 or P<0.01).

Conclusion: The expression of TLR2/4mRNA is increased and hepatic injuries are aggravated in the liver of AHNP rats. TLR2/4mRNA gene expression in the liver of AHNP rats can be markedly inhibited by NO, leading to the relief of hepatic injuries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Amylases / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Hemorrhage / metabolism*
  • Humans
  • Liver / metabolism*
  • Male
  • Nitric Oxide / metabolism*
  • Pancreatitis, Acute Necrotizing / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • RNA, Messenger
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Amylases