Suppression of Nuclear Factor-κB Activity in Kupffer Cells Protects Rat Liver Graft From Ischemia-Reperfusion Injury

• Published in: Transplantation proceedings Vol. 42; no. 5; pp. 1582 - 1586
• Main Authors: Li, J.D, Peng, Y, Peng, X.Y, Li, Q.L, Li, Q
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.06.2010; Elsevier
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastroenterology. Liver. Pancreas. Abdomen; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Other diseases. Semiology; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Rat; Suppression; Rodentia; Cardiovascular disease; Hepatic disease; Transplantation; Biological activity; Vascular disease; Medicine; Kupffer cell; Vertebrata; Mammalia; Treatment; Animal; Surgery; Hepatic ischemia reperfusion injury; Digestive diseases; Graft; Non specific immunity; Transcription factor NFκB; Protection
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2009.12.077

Abstract Objective The objective of this study was to investigate the protective effect and mechanisms of nuclear factor (NF)-κB decoy oligodeoxynucleotides (ODN) on rat liver grafts following ischemia-reperfusion injury (IRI). Methods Animals were randomly divided into 3 groups (n = 8): control ischemia-reperfusion (IR) and decoy ODN groups; in the last cohort donor grafts were transfected with 120 μg NF-κB decoy ODN before procurement. Following 2 hours of reperfusion, NF-κB binding activity was detected in isolated Kupffer cells (KCs) using electrophoretic mobility shift assays (EMSA). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 messenger RNA (mRNA) expressions were analyzed using reverse transcriptase polymerase chain reaction (RT-PCR) methods. Liver tissue and blood serum were collected for histopathologic examination and liver function test, respectively. Results The NF-κB binding activity, TNF-α and IL-6 mRNA expression as well as serum ALT and total bilirubin levels were significantly increased compared with the control group following reperfusion ( P < .01). A large number of hepatocytes showed degeneration and necrosis. However, these indices were significantly ameliorated among the decoy ODN group ( P < .01) with preserved hepatic lobule architecture. Conclusion KCs NF-κB activation following reperfusion plays an important role in IRI after liver transplantation. The decoy strategy showed an apparent effect to suppress NF-κB activation and inhibit production of downstream cytokines, thereby protecting liver grafts from IRI.