Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune-mediated liver injury.
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Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune-mediated liver injury. / Sass, Gabriele; Seyfried, Stefan; Miguel, Parreira Soares; Yamashita, Kenichiro; Kaczmarek, Elzbieta; Neuhuber, Winfried L; Tiegs, Gisa.
in: HEPATOLOGY, Jahrgang 40, Nr. 5, 5, 2004, S. 1128-1135.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune-mediated liver injury.
AU - Sass, Gabriele
AU - Seyfried, Stefan
AU - Miguel, Parreira Soares
AU - Yamashita, Kenichiro
AU - Kaczmarek, Elzbieta
AU - Neuhuber, Winfried L
AU - Tiegs, Gisa
PY - 2004
Y1 - 2004
N2 - Induction of the heme-degrading enzyme heme oxygenase-1 (HO-1) has been shown to be beneficial in terms of improvement of liver allograft survival and prevention of CD95-mediated apoptosis in the liver. In the present study, we investigated the effects of HO-1, and its products carbon monoxide (CO), biliverdin (BV), and iron/ferritin, in a mouse model of inflammatory liver damage inducible by lipopolysaccharide (LPS) in mice sensitized with the hepatocyte-specific transcription inhibitor D-galactosamine (GalN). Our results show that HO-1 induction by cobalt-protoporphyrin-IX (CoPP) reduced cytokine expression, protected mice from liver injury, and prolonged survival. While in contrast to ferritin overexpression, single administration of the CO donor methylene chloride (MC) or of BV also protected mice from liver damage, only coadministration of both HO products prolonged survival and reduced the expression of cytokines, e.g., tumor necrosis factor (TNF) and interferon gamma (IFN-gamma). In conclusion, HO-1-induced prolongation of survival, but not the protection from liver damage, seems to be dependent on down-regulation of cytokine synthesis.
AB - Induction of the heme-degrading enzyme heme oxygenase-1 (HO-1) has been shown to be beneficial in terms of improvement of liver allograft survival and prevention of CD95-mediated apoptosis in the liver. In the present study, we investigated the effects of HO-1, and its products carbon monoxide (CO), biliverdin (BV), and iron/ferritin, in a mouse model of inflammatory liver damage inducible by lipopolysaccharide (LPS) in mice sensitized with the hepatocyte-specific transcription inhibitor D-galactosamine (GalN). Our results show that HO-1 induction by cobalt-protoporphyrin-IX (CoPP) reduced cytokine expression, protected mice from liver injury, and prolonged survival. While in contrast to ferritin overexpression, single administration of the CO donor methylene chloride (MC) or of BV also protected mice from liver damage, only coadministration of both HO products prolonged survival and reduced the expression of cytokines, e.g., tumor necrosis factor (TNF) and interferon gamma (IFN-gamma). In conclusion, HO-1-induced prolongation of survival, but not the protection from liver damage, seems to be dependent on down-regulation of cytokine synthesis.
KW - Animals
KW - Survival Analysis
KW - Mice
KW - Mice, Inbred BALB C
KW - Gene Transfer Techniques
KW - Drug Synergism
KW - Membrane Proteins
KW - Heme Oxygenase-1
KW - Biliverdine/pharmacology
KW - Carbon Monoxide/pharmacology
KW - Cytokines/antagonists & inhibitors
KW - Drug-Induced Liver Injury/immunology/physiopathology
KW - Ferritins/genetics/pharmacology
KW - Galactosamine/immunology
KW - Heme Oxygenase (Decyclizing)/biosynthesis
KW - Immune System Diseases/complications
KW - Immunization
KW - Interferon-gamma/antagonists & inhibitors
KW - Lipopolysaccharides
KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors
KW - Animals
KW - Survival Analysis
KW - Mice
KW - Mice, Inbred BALB C
KW - Gene Transfer Techniques
KW - Drug Synergism
KW - Membrane Proteins
KW - Heme Oxygenase-1
KW - Biliverdine/pharmacology
KW - Carbon Monoxide/pharmacology
KW - Cytokines/antagonists & inhibitors
KW - Drug-Induced Liver Injury/immunology/physiopathology
KW - Ferritins/genetics/pharmacology
KW - Galactosamine/immunology
KW - Heme Oxygenase (Decyclizing)/biosynthesis
KW - Immune System Diseases/complications
KW - Immunization
KW - Interferon-gamma/antagonists & inhibitors
KW - Lipopolysaccharides
KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors
M3 - SCORING: Journal article
VL - 40
SP - 1128
EP - 1135
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
IS - 5
M1 - 5
ER -
