• Ying-Hsien Huang, Pei-Wen Wang, Mao-Meng Tiao, Ming-Huei Chou, Yung-Ying Du, Chao-Cheng Huang, and Jiin-Haur Chuang.
• Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
• J. Surg. Res. 2011 Sep 1; 170 (1): e47-55.

BackgroundObstructive 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 MethodsA 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.ResultsObstructive 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.ConclusionsThe 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.Copyright © 2011 Elsevier Inc. All rights reserved.

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