Role of NF-kappaB in liver ischemia reperfusion injury of rats

Abstract

To determine the role of NF-kappaB in ischemia reperfusion (I/R) injury of the rat liver, rats underwent partial hepatic ischemia and reperfusion. The left and median lobes of the liver were subjected to ischemia for 90 min followed by reperfusion for defined times. NF-kappaB activity was analyzed by electrophoretic mobility shift assay (EMSA). Semiquantitative reverse-transcriptase polymerase chain reaction was used to analyze TNF-α and ICAM-1 mRNA levels. Results showed during liver I/R injury, NF-kappaB activation was induced in a time dependent manner. NF-kappaB was activated within 1 h and 2 h after the initiation of reperfusion and decreased after 4 h. Messenger RNA expression of TNF-α and ICAM-1 were increased after the reperfusion of 2 h. It was concluded that during hepatic I/R injury, NF-kappaB was activated and could bind to special sequence in the promoters of budget genes, which can up-regulate the expression of TNF-α and ICAM-1 mRNA to result in ischemia reperfusion injury of the rat liver.

Keywords

NF-kappaB / liver / Ischemia reperfusion injury

References

[1] JaeschkeH, ForhoodA. Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol, 1991, 260G355-G355

[2] CollettiL M, RemickD G, KunkelS L, et al. . Role of tumor necrosis factor-α in the pathophysiologic alternations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest, 1990, 851936-1936

[3] SunZ W, AnderssonR. NF-[kappa]B activation and inhibition: A review. Shock, 2002, 18(2): 99-99

[4] PeraltaD C, HotterG. Liver ischemic preconditioning is mediated by the inhibitory action of nitric oxide on endothelin. Biochem Biophysio Res Commun, 1996, 229(1): 264-264

[5] DeryckereF, GannonF. A one-hour minipreparation technique for extraction of DNA-binding proteins from animal tissues. Biotechmques, 1994, 16398-398

[6] CollettiL M, RemickD G, BurtchG D, et al. . Role of tumor necrosis factor-α in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest, 1990, 851936-1936

[7] FarhoodA, McGuireG M, ManningA M, et al. . Intercelluar adhesion molecule 1 (ICAM-1) expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver. J Leukoc Biol, 1995, 57368-368

[8] HuguetC, GavelliA, BonaS. Hepatic resection with ischemia of the liver exceeding one hour. J Am Coll Surg, 1994, 178454-454

[9] LiuD L, JeppssonB, HakanssonC H, et al. . Multiplesystem organ damage resulting from prolonged hepatic inflow interruption. Arch Surg, 1996, 131442-442

[10] GonzalezF X, RimolaA, GrandeL, et al. . Predictive factors of early postoperative graft function in human liver transplantation. Hepatology, 1994, 20565-565

[11] CollettiL M, CortisA, LukacsN, et al. . Tumor necrosis factor up-regulates intercellular adhesion molecule 1, which is important in the neutrophil-dependent lung and liver injury associated with hepatic ischemia and reperfusion in the rat. Shock, 1998, 10182-182

[12] LentschA B, YoshidomeH, CheadleW G, et al. . Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and KC. Hepatology, 1998, 271172-1172

[13] GhoshS, MayM J, KoppE B. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune response. Annu Rev Immunol, 1998, 16225-225

[14] CollettiL M, KunkelS L, WalzA, et al. . Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein. J Clin Invest, 1995, 95134-134