HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat

Histochem Cell Biol. 2011 May;135(5):443-52. doi: 10.1007/s00418-011-0802-6. Epub 2011 Mar 24.

Abstract

High mobility group box 1 (HMGB1) acts as an early mediator in inflammation and organ injury. Ischemia reperfusion (I/R) injury induces HMGB1 translocation and expression in ischemic areas. However, it is unknown whether selective warm liver I/R injury also induces the expression of HMGB1 in non-ischemic lobes. The present study aimed to test the hypothesis that selective liver I/R injury also causes HMGB1 translocation and up-regulates its expression in non-ischemic liver areas. In the present study, selective I/R injury was induced by clamping the median and left lateral liver lobes for 90 min followed by 0.5, 6 and 24 h reperfusion. We used male inbred Lewis rats; six animals for each point in time and six animals for the normal control group. Selective hepatic I/R injury induced morphological changes not only in ischemic lobes but also in non-ischemic lobes. HMGB1 translocation and expression was increased in a time-dependent manner in the ischemic lobes, and increased in with delayed onset in the non-ischemic lobes. Serum HMGB1 levels were increased after reperfusion. Furthermore, liver I/R injury up-regulated the expression of HMGB1 receptors (Toll-like receptor 4 and receptor for advanced glycation end products and pro-inflammatory cytokines (Tumor necrosis factor-alpha and interleukin-6) in both ischemic lobes, however, the up-regulation of these cytokines was more prominent in the ischemic lobes. In conclusion, selective warm I/R induces a substantial "sympathetic/bystander" effect on the non-ischemic lobes in terms of HMGB1 translocation and local cytokine production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • HMGB1 Protein / analysis
  • HMGB1 Protein / metabolism*
  • Immunohistochemistry
  • Ischemia / blood
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Liver / blood supply
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Polymerase Chain Reaction
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury / blood
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology

Substances

  • HMGB1 Protein
  • Hbp1 protein, rat