CXC chemokine expression after stimulation with interferon-gamma in primary rat hepatocytes in culture

Shock. 2002 Jun;17(6):513-20. doi: 10.1097/00024382-200206000-00013.

Abstract

Monokine-induced by gamma interferon (MIG) and gamma-interferon-inducible protein (IP-10) are members of the CXC chemokine family that have been shown to be induced by interferon-gamma (IFNy) in some cell types. The purpose of this investigation was to determine whether IFNgamma influences CXC chemokine production, particularly MIG and IP-10, in primary rat hepatocytes in culture. Previous experiments in our laboratory have demonstrated that pharmacologic doses of IFNgamma in an in vivo model of hepatic ischemia/reperfusion-induced liver injury resulted in increased hepatic levels of IP-10 and MIG and decreased hepatic levels of macrophage inflammatory protein-2, Kupffer cells, and epithelial neutrophil-activating protein, with a concomitant decrease in neutrophil-mediated hepatic injury. In the current investigation, MIG and IP-10 mRNA and protein were up-regulated in primary rat hepatocytes in vitro in response to IFNgamma. Although MIG and IP-10 mRNA were both somewhat increased at early time points, larger increases in these chemokines were seen at later time points, specifically at 24, 48, and 72 h of incubation as compared to controls. Levels of Kupffer cells and macrophage inflammatory protein-2 mRNA after IFNgamma were negligible and similar to those seen in controls. These findings were confirmed by enzyme-linked immunosorbent assay analysis. These studies demonstrate that IFNgamma in vitro up-regulates the production of MIG and IP-10, at both the mRNA and protein levels.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokine CXCL2
  • Chemokine CXCL9
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Chemokines, CXC / biosynthesis*
  • Chemokines, CXC / chemistry
  • Chemokines, CXC / genetics
  • Chemotactic Factors / biosynthesis
  • Chemotactic Factors / genetics
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Dexamethasone / pharmacology
  • Gene Expression / drug effects
  • Hepatocytes / drug effects*
  • Hepatocytes / immunology*
  • Hepatocytes / metabolism
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Interferon-gamma / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CXCL1 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokine CXCL2
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, rat
  • Cxcl2 protein, rat
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • keratinocyte-derived chemokines
  • Dexamethasone
  • Interferon-gamma