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Fibronectin prevents D-galactosamine/lipopolysaccharide-induced lethal hepatic failure in mice.

Abstract

Plasma fibronectin (FN) has a broad range of biological functions involved in cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, reticuloendothelial system function, and ischemic injury. In this study, we examined the effects of FN on D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant liver failure in mice. Female Balb/c mice received intraperitoneal injection of 50 mug/kg of LPS and 400 mg/kg of GalN simultaneously. Thirty minutes before GalN/LPS administration, human plasma FN (FN group) or the same dose of human serum albumin (control group) was given intravenously. GalN/LPS induced a marked decrease in plasma FN, which was reversed by FN pretreatment. The survival rate of the FN group was markedly improved in a dose-dependent manner compared with that of the control group (survival rate 0%). FN prevented increases in the concentrations of serum enzymes and total bilirubin related to liver injury. FN pretreatment significantly suppressed tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 levels, and enhanced IL-10 levels in serum and liver tissue compared with the control group. Moreover, TUNEL staining, caspase 3 and 8 activities, and necrosis in the remnant liver were significantly decreased in the FN-treated rats compared with the controls. Furthermore, FN pretreatment inhibited the activation of nuclear factor (NF)-kappaB and increased the expression of Bcl-xL protein in liver tissue. These results suggest that FN protected against GalN/LPS-induced liver failure by a mechanism involving inhibition of NF-kappaB activation, which caused down-regulation of TNF-alpha and involved up-regulation of IL-10, and elevation of Bcl-xL induced a blockage of apoptotic signals, by which apoptosis of hepatocytes caused by GalN/LPS was suppressed.

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  • Authors+Show Affiliations

    ,

    Department of Surgery, Kansai Medical University, Osaka 570-8507, Japan.

    , , , ,

    Source

    Shock (Augusta, Ga.) 25:1 2006 Jan pg 80-7

    MeSH

    Animals
    Apoptosis
    Cytokines
    Female
    Fibronectins
    Galactosamine
    Gene Expression Regulation
    Hepatocytes
    Lipopolysaccharides
    Liver
    Liver Failure
    Mice
    Mice, Inbred BALB C
    NF-kappa B
    Necrosis
    Signal Transduction
    bcl-X Protein

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    16369191

    Citation

    Qiu, Zeyu, et al. "Fibronectin Prevents D-galactosamine/lipopolysaccharide-induced Lethal Hepatic Failure in Mice." Shock (Augusta, Ga.), vol. 25, no. 1, 2006, pp. 80-7.
    Qiu Z, Kwon AH, Tsuji K, et al. Fibronectin prevents D-galactosamine/lipopolysaccharide-induced lethal hepatic failure in mice. Shock. 2006;25(1):80-7.
    Qiu, Z., Kwon, A. H., Tsuji, K., Kamiyama, Y., Okumura, T., & Hirao, Y. (2006). Fibronectin prevents D-galactosamine/lipopolysaccharide-induced lethal hepatic failure in mice. Shock (Augusta, Ga.), 25(1), pp. 80-7.
    Qiu Z, et al. Fibronectin Prevents D-galactosamine/lipopolysaccharide-induced Lethal Hepatic Failure in Mice. Shock. 2006;25(1):80-7. PubMed PMID: 16369191.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Fibronectin prevents D-galactosamine/lipopolysaccharide-induced lethal hepatic failure in mice. AU - Qiu,Zeyu, AU - Kwon,A-Hon, AU - Tsuji,Katsushige, AU - Kamiyama,Yasuo, AU - Okumura,Tadayoshi, AU - Hirao,Yutaka, PY - 2005/12/22/pubmed PY - 2006/5/11/medline PY - 2005/12/22/entrez SP - 80 EP - 7 JF - Shock (Augusta, Ga.) JO - Shock VL - 25 IS - 1 N2 - Plasma fibronectin (FN) has a broad range of biological functions involved in cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, reticuloendothelial system function, and ischemic injury. In this study, we examined the effects of FN on D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant liver failure in mice. Female Balb/c mice received intraperitoneal injection of 50 mug/kg of LPS and 400 mg/kg of GalN simultaneously. Thirty minutes before GalN/LPS administration, human plasma FN (FN group) or the same dose of human serum albumin (control group) was given intravenously. GalN/LPS induced a marked decrease in plasma FN, which was reversed by FN pretreatment. The survival rate of the FN group was markedly improved in a dose-dependent manner compared with that of the control group (survival rate 0%). FN prevented increases in the concentrations of serum enzymes and total bilirubin related to liver injury. FN pretreatment significantly suppressed tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 levels, and enhanced IL-10 levels in serum and liver tissue compared with the control group. Moreover, TUNEL staining, caspase 3 and 8 activities, and necrosis in the remnant liver were significantly decreased in the FN-treated rats compared with the controls. Furthermore, FN pretreatment inhibited the activation of nuclear factor (NF)-kappaB and increased the expression of Bcl-xL protein in liver tissue. These results suggest that FN protected against GalN/LPS-induced liver failure by a mechanism involving inhibition of NF-kappaB activation, which caused down-regulation of TNF-alpha and involved up-regulation of IL-10, and elevation of Bcl-xL induced a blockage of apoptotic signals, by which apoptosis of hepatocytes caused by GalN/LPS was suppressed. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/16369191/Fibronectin_prevents_D_galactosamine/lipopolysaccharide_induced_lethal_hepatic_failure_in_mice_ L2 - http://Insights.ovid.com/pubmed?pmid=16369191 DB - PRIME DP - Unbound Medicine ER -