title: Time course profile and cell-type-specific production of monokine induced by interferon-gamma in Concanavalin A-induced hepatic injury in mice: comparative study with interferon-inducible protein-10.
abstract: BACKGROUND
  We have previously shown that interferon-inducible protein-10 (IP-10), a chemokine for activated lymphocytes, was specifically induced in the liver of Concanavalin A (Con A)-treated mice. The aim of this study was to investigate the time course profile and cell-type-specific hepatic production of monokine induced by interferon-gamma (MIG), a chemokine which shares its receptor and most of its activity with IP-10, in Con A-treated mice and to compare them with those of IP-10.
  
  
  METHODS
  Hepatic mRNA expression of MIG and IP-10 was studied by means of Northern blot analysis and in situ hybridization in Con A-treated mice. The levels of MIG and IP-10 in the serum and culture supernatants of murine hepatoma-, hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage-derived cell lines were determined by means of specific enzyme-linked immunosorbent assays.
  
  
  RESULTS
  The serum level of MIG slowly reached a maximum at 12 h after Con A injection and remained elevated for a long time, whereas that of IP-10 reached a maximum at 3 h and declined quickly, a finding supported by Northern blot analysis. Using in situ hybridization, the mRNA of MIG as well as IP-10 was found to be expressed in hepatocytes and hepatic non-parenchymal cells. Similar to IP-10, MIG was produced by hepatoma-, hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage-derived cell lines in vitro.
  
  
  CONCLUSIONS
  Although both MIG and IP-10 were produced by hepatocytes and hepatic non-parenchymal cells in Con A-treated mice, the time course profile of MIG was distinguishable from that of IP-10. The fact that hepatic MIG and IP-10 were produced sequentially in this hepatitis model may suggest that a non-redundant role is played by these two chemokines in the process of hepatic necro-inflammation.
authors.affiliation: Third Dept. of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. yitoh@sun.kpu-m.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Itoh
authors.forename: A
authors.initials: A
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Nishioji
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Kirishima
authors.forename: T
authors.initials: T
authors.lastname: Toyama
authors.forename: N
authors.initials: N
authors.lastname: Yamauchi
authors.forename: Y
authors.initials: Y
authors.lastname: Nagao
authors.forename: S
authors.initials: S
authors.lastname: Narumi
authors.forename: T
authors.initials: T
authors.lastname: Okanoue
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism*; D003208:Concanavalin A; D004797:Enzyme-Linked Immunosorbent Assay; D006520:Hepatitis, Animal / Q000378:metabolism*; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
chemical_list: C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D003208:Concanavalin A; D007371:Interferon-gamma