Glucocorticoid modulates high-mobility group box 1 expression and toll-like receptor activation in obstructive jaundice

Ying Hsien Huang, Pei Wen Wang, Mao Meng Tiao, Ming Huei Chou, Yung Ying Du, Chao Cheng Huang, Jiin Haur Chuang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

17 Scopus citations

Abstract

Background: Obstructive jaundice is associated with bacterial translocation and inflammatory cytokine induction. It is unknown if toll-like receptors (TLRs) and their upstream molecule high mobility group box-1 (HMGB1) are involved in the pathogenetic mechanism and if glucocorticoid is effective in modulating the process. Materials and Methods: A rat model of cholestasis by ligation of the extrahepatic bile duct (BDL) for 2 wk was created. TLRs, interferon regulatory factors (IRFs), IL-6, IL-8, antimicrobial peptide β-defensin, and cathelicidin, as well as HMGB1 expressions were studied by using real-time quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). Glucocorticoid treatment was applied to a group of BDL rats. Results: Obstructive jaundice for 2 wk was associated with significant up-regulation of TLR1, 2, 4, 6, 7, and 9 mRNA expressions. There were significant increases of liver IRF5, IL-6, and β-defensin 1 mRNA levels in the BDL rats than in the sham and nonoperative control rats, which were associated with significant increase of immunoreactive IRF5 protein staining in the nucleus of Kupffer cells and neutrophils. Hepatic HMGB1 expression and release into serum were significantly elevated in the cholestatic rats than in the sham and control rats. Glucocorticoid treatment significantly decreased hepatic HMGB1 expression and release into serum, which was associated with significantly decreased hepatic TLR4 mRNA expression in the cholestatic rats. Conclusions: The results indicate that obstructive jaundice may induce hepatic HMGB1 expression with activation of TLR4 and a number of downstream signaling molecules, which can be reversed by glucocorticoid administration.

Original languageEnglish
Pages (from-to)e47-e55
JournalJournal of Surgical Research
Volume170
Issue number1
DOIs
StatePublished - 09 2011

Keywords

  • Toll-like receptor
  • high-mobility group box 1
  • interferon
  • interferon regulatory factor
  • obstructive jaundice

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