Retarded liver growth in interleukin-6-deficient and tumor necrosis factor receptor-1-deficient mice.

The liver size in adult mammals is tightly regulated in relation to body weight, but the hormonal control of this is largely unknown. We investigated the roles of interleukin-6 (IL-6) and tumor necrosis factor (TNF) receptor-1 in the regulation of intact liver weight in adult mice. The relative liver wet and dry weights of older adult (5- to 10-month-old) IL-6 knockout (IL-6(-/-)) mice were decreased by 22-28%, and total contents of DNA and protein were decreased compared with those in age-matched wild-type mice. Weights of other visceral organs were unaffected. Older adult (6- to 8-month-old) TNF receptor-1 knockout (TNFR1(-/-)) mice displayed decreased relative liver weight. Treatment with a single injection of IL-6 increased liver wet and dry weights in IL-6(-/-) and wild-type mice, but not TNFR1(-/-) mice. Treatment with TNFalpha enhanced liver weight and DNA synthesis of nonparenchymal liver cells at 24 h in wild-type, but not IL-6(-/-), mice. At 48 h, TNFalpha induced DNA synthesis in nonparenchymal cells and hepatocytes of both wild-type and IL-6(-/-) mice. In conclusion, TNF receptor-1 stimulation and IL-6 production are both necessary for normal liver weight gain in older adult mice. The results of TNFalpha and IL-6 treatment further indicate that the effects of TNF receptor-1 and IL-6 depend on each other for full stimulation of liver growth.

[1]  J. Jansson,et al.  Normal pharmacologically-induced, but decreased regenerative liver growth in interleukin-6-deficient (IL-6(-/-)) mice. , 2000, Journal of hepatology.

[2]  A. Fornace,et al.  Death and decoy receptors and p53-mediated apoptosis , 2000, Leukemia.

[3]  K. Sjögren,et al.  Disproportional skeletal growth and markedly decreased bone mineral content in growth hormone receptor -/- mice. , 2000, Biochemical and biophysical research communications.

[4]  D. Leroith,et al.  Normal growth and development in the absence of hepatic insulin-like growth factor I. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Sjögren,et al.  Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. Demetris,et al.  Mitosis and apoptosis in the liver of interleukin‐6–deficient mice after partial hepatectomy , 1999, Hepatology.

[7]  C. Lowenstein,et al.  Impaired liver regeneration in inducible nitric oxide synthasedeficient mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  P. Galtier,et al.  Peroxisome Proliferator-activated Receptor α-Isoform Deficiency Leads to Progressive Dyslipidemia with Sexually Dimorphic Obesity and Steatosis* , 1998, The Journal of Biological Chemistry.

[9]  P. Schirmacher,et al.  Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. , 1998, The American journal of pathology.

[10]  N. Fausto,et al.  Deficient liver regeneration after carbon tetrachloride injury in mice lacking type 1 but not type 2 tumor necrosis factor receptor. , 1998, The American journal of pathology.

[11]  T. Hirano.  Interleukin 6 and its receptor: ten years later. , 1998, International reviews of immunology.

[12]  T. Wagner,et al.  A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Schirmacher,et al.  Soluble IL-6 receptor leads to a paracrine modulation of the IL-6-induced hepatic acute phase response in double transgenic mice. , 1997, Journal of immunology.

[14]  J. Peschon,et al.  Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G. Michalopoulos,et al.  Liver Regeneration , 1997, Science.

[16]  J. Ljubimova,et al.  Fulminant hepatic failure in rats: Survival and effect on blood chemistry and liver regeneration , 1996, Hepatology.

[17]  E. Furth,et al.  Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice , 1996, Science.

[18]  J. Rubin,et al.  Hepatocyte growth factor/scatter factor overexpression induces growth, abnormal development, and tumor formation in transgenic mouse livers. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[19]  A. Columbano,et al.  Liver regeneration versus direct hyperplasia , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  R. Taub.  Transcriptional control of liver regeneration , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  R. Rai,et al.  Regulation of signal transduction during liver regeneration , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  Carmen Birchmeier,et al.  Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud , 1995, Nature.

[23]  M. Sharpe,et al.  Scatter factor/hepatocyte growth factor is essential for liver development , 1995, Nature.

[24]  R. Schwall,et al.  Induction of liver growth in normal mice by infusion of hepatocyte growth factor/scatter factor. , 1995, The American journal of physiology.

[25]  G. Merlino,et al.  Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice. , 1994, The American journal of pathology.

[26]  R. Zinkernagel,et al.  Impaired immune and acute-phase responses in interleukin-6-deficient mice , 1994, Nature.

[27]  A. Hsueh,et al.  Gonadotropin-releasing hormone directly induces apoptotic cell death in the rat ovary: biochemical and in situ detection of deoxyribonucleic acid fragmentation in granulosa cells. , 1994, Endocrinology.

[28]  T. Mak,et al.  Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection , 1993, Cell.

[29]  David C. Lee,et al.  TGFα deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice , 1993, Cell.

[30]  C. McClain,et al.  Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. , 1992, The American journal of physiology.

[31]  E. Chen,et al.  Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  R. Palmiter,et al.  Expression of insulin-like growth factor I stimulates normal somatic growth in growth hormone-deficient transgenic mice. , 1990, Endocrinology.

[33]  R. Hammer,et al.  Growth allometry of the organs in giant transgenic mice. , 1987, Endocrinology.

[34]  B. Jeppsson,et al.  Portal branch ligation in the rat. Reevaluation of a model. , 1986, The American journal of pathology.

[35]  W. Russell.  Growth Hormone, Somatomedins, and the Liver , 1985, Seminars in liver disease.

[36]  M. Preece,et al.  Effect of bovine growth hormone and a partially pure preparation of somatomedin on various growth parameters in hypopituitary dwarf mice. , 1981, The Journal of endocrinology.

[37]  K. Weinbren,et al.  THE MITOTIC RESPONSE IN THE RAT LIVER AFTER DIFFERENT REGENERATIVE STIMULI. , 1964, British journal of experimental pathology.