Involvement of Fas/Fas ligand system‐mediated apoptosis in the development of concanavalin A‐induced hepatitis

Concanavalin A (Con A)‐induced hepatitis is an experimental hepatitis model in which hepatic injury is caused by the action of cytokines produced by T cells. Using IFN‐γ‐deficient mice, we previously demonstrated that IFN‐γ plays a central role in Con A‐induced hepatitis. Here, we show that development of the disease is completely suppressed in gld/gld mice, in which Fas ligand is defective. In contrast, suppression of the disease in lpr/lpr mice was incomplete, since a small amount of the fas mRNA was produced in these mice. The data indicate that activation of the Fas/Fas ligand system is a necessary step in the development of Con A‐induced hepatitis. Furthermore, we found that not only fas but also caspase‐1 expression was reduced in IFN‐γ‐deficient mice. Since caspase‐1 is an integral component of Fas signal transduction, these observations suggest that IFN‐γ‐induced activation of both fas and caspase‐1 expression causes enhancement of hepatocyte apoptosis resulting in the development of hepatitis.

[1]  P. Galle,et al.  Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1 /Fas) Mediated apoptosis , 1998, Nature Medicine.

[2]  L. Moldawer,et al.  Disparate Roles for TNF-α and Fas Ligand in Concanavalin A-Induced Hepatitis , 1998, The Journal of Immunology.

[3]  R. Silverman,et al.  Interferon action and apoptosis are defective in mice devoid of 2′,5′‐oligoadenylate‐dependent RNase L , 1997, The EMBO journal.

[4]  K. Takeda,et al.  Contribution of Fas ligand to T cell-mediated hepatic injury in mice. , 1997, Gastroenterology.

[5]  Y. Iwakura,et al.  Suppression of concanavalin A-induced hepatitis in IFN-gamma(-/-) mice, but not in TNF-alpha(-/-) mice: role for IFN-gamma in activating apoptosis of hepatocytes. , 1997, Journal of immunology.

[6]  R. Kamen,et al.  Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production , 1997, Nature.

[7]  M. Su,et al.  Activation of Interferon-γ Inducing Factor Mediated by Interleukin-1β Converting Enzyme , 1997, Science.

[8]  H. Mohri,et al.  Interferon-γ InducesIceGene Expression and Enhances Cellular Susceptibility to Apoptosis in the U937 Leukemia Cell Line ☆ , 1996 .

[9]  G. Gerken,et al.  Role of sinusoidal endothelial cells of the liver in concanavalin A‐induced hepatic injury in mice , 1996, Hepatology.

[10]  T. Akaike,et al.  Concanavalin A induces perforin‐mediated but not Fas‐mediated hepatic injury , 1996, Hepatology.

[11]  N. Copeland,et al.  Molecular characterization of mouse and rat CPP32β gene encoding a cysteine protease resembling interleukin-1β converting enzyme and CED-3 , 1996 .

[12]  H. Fujiwara,et al.  Critical involvement of interferon γ in the pathogenesis of T‐cell activation‐associated hepatitis and regulatory mechanisms of interleukin‐6 for the manifestations of hepatitis , 1996, Hepatology.

[13]  N. Yoshida,et al.  Enhanced and accelerated lymphoproliferation in Fas-null mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Galle,et al.  Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage , 1995, The Journal of experimental medicine.

[15]  T. Akaike,et al.  Protective effect of hepatocyte growth factor on interferon‐gamma—induced cytotoxicity in mouse hepatocytes , 1995, Hepatology.

[16]  N. Ishimura,et al.  The expression of IL‐2, IL‐4 and interferon‐gamma (IFN‐γ) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B , 1995, Clinical and experimental immunology.

[17]  S. Nagata,et al.  Involvement of an ICE-like protease in Fas-mediated apoptosis , 1995, Nature.

[18]  M. Su,et al.  Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. , 1995, Science.

[19]  R. Kamen,et al.  Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock , 1995, Cell.

[20]  M. Gershwin,et al.  Cytokine patterns and cytotoxic mediators in primary biliary cirrhosis , 1995, Hepatology.

[21]  M. Leist,et al.  Concanavalin A—induced T‐cell—mediated hepatic injury in mice: The role of tumor necrosis factor , 1995, Hepatology.

[22]  N. Hayashi,et al.  Role of Fas ligand in apoptosis induced by hepatitis C virus infection. , 1994, Biochemical and biophysical research communications.

[23]  C. Thompson,et al.  bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria. , 1994, Development.

[24]  T. Taniguchi,et al.  Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1 , 1994, Cell.

[25]  E. O’Neill,et al.  T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6 , 1994, The Journal of experimental medicine.

[26]  N. Jenkins,et al.  Generalized lymphoproliferative disease in mice, caused by a point mutation in the fas ligand , 1994, Cell.

[27]  S. B. Lee,et al.  The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis. , 1994, Virology.

[28]  Junying Yuan,et al.  Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3 , 1993, Cell.

[29]  S. Korsmeyer,et al.  Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death , 1993, Cell.

[30]  J. Mountz,et al.  Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene , 1993, The Journal of experimental medicine.

[31]  K. Elkon,et al.  The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn , 1993, The Journal of experimental medicine.

[32]  S. Nagata,et al.  Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[33]  S. Ben‐Sasson,et al.  Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation , 1992, The Journal of cell biology.

[34]  A. Wendel,et al.  A T cell-dependent experimental liver injury in mice inducible by concanavalin A. , 1992, The Journal of clinical investigation.

[35]  N. Copeland,et al.  Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis , 1992, Nature.

[36]  N. Copeland,et al.  The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. , 1992, Journal of immunology.

[37]  K. Yoshioka,et al.  Tumor necrosis factor α production by peripheral blood mononuclear cells of patients with chronic liver disease , 1989 .

[38]  K. Yoshioka,et al.  Tumor necrosis factor alpha production by peripheral blood mononuclear cells of patients with chronic liver disease. , 1989, Hepatology.

[39]  G. Alexander,et al.  Interleukin-1 and interleukin-2 activity in chronic hepatitis B virus infection. , 1988, Gastroenterology.

[40]  M. Negrini,et al.  Molecular analysis of mbcl-2: Structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma , 1987, Cell.

[41]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[42]  J. Kerr,et al.  The significance of cell death by apoptosis in hepatobiliary disease , 1987 .

[43]  D. Goeddel,et al.  Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[44]  D. Goeddel,et al.  Cloning and expression of murine immune interferon cDNA. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Kerr,et al.  THE NATURE OF PIECEMEAL NECROSIS IN CHRONIC ACTIVE HEPATITIS , 1979, The Lancet.

[46]  G. Guidi,et al.  A new colorimetric ultramicromethod for serum glutamic-oxalacetic and glutamic-pyruvic transaminase determination. , 1970, Clinica chimica acta; international journal of clinical chemistry.

[47]  A. Kimchi,et al.  Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death. , 1995, Genes & development.

[48]  N. Peterslund,et al.  Acvclovir in herpes zoster. , 1981 .