Endotoxin Tolerance Attenuates Liver Ischemia/Reperfusion Injury by Down-Regulation of Interleukin-1 Receptor-Associated Kinase 4 in Kupffer Cells

Abstract

Aim The aim of this study was to study the role of interleukin-1 receptor-associated kinase 4 (IRAK-4) in the formation of endotoxin tolerance (ET) in liver ischemia/reperfusion (I/R) injury. Methods Animals were randomly divided into 3 groups: control group, I/R group, and ET group. Liver morphological changes were observed using optical microscopy with hematoxylin eosin (HE) staining. Alanine aminotransferase (ALT) was quantified to measure liver functional injury. The messenger RNA (mRNA) and protein expressions of IRAK-4 in Kupffer cells (KCs) isolated from recipients were detected using real-time polymerase chain reaction (PCR) and Western blot, respectively. The activities of NF-κB and the supernatant levels of tumor necrosis factor-alpha (TNF-α), IL-10 were assayed using enzyme-linked immunosorbent assay (ELISA). Results Endotoxin preconditioning improved hepatic tissue injury as indicated by morphological analysis, whereas serum ALT levels were significantly decreased at various times ( P < .05); concurrently, the expression of IRAK-4 and TNF-α in KCs was down-regulated ( P < .05) and the secretion of IL-10 was enhanced ( P < .05); NF-κB DNA-binding activity of KCs was also significantly inhibited by endotoxin preconditioning ( P < .05). Conclusion Endotoxin preconditioning attenuated the liver I/R injury caused by transplantation. The expression of IRAK-4 in KCs may play an important role in the formation of ET.