title: CXC chemokine expression after stimulation with interferon-gamma in primary rat hepatocytes in culture.
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.
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor 48109, USA.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Ren
authors.forename: Audra
authors.initials: A
authors.lastname: Kennedy
authors.forename: Lisa Marie
authors.initials: LM
authors.lastname: Colletti
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D054370:Chemokine CXCL9; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C475829:CXCL1 protein, human; C080810:CXCL9 protein, human; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C074302:keratinocyte-derived chemokines; D003907:Dexamethasone; D007371:Interferon-gamma