title: Differential gene expression of CINC, NOS II, and ICAM-1 in endotoxemic liver cells by rG-CSF.
abstract: BACKGROUND
  We have recently demonstrated that recombinant granulocyte colony-stimulating factor (rG-CSF) modulates lipopolysaccharide (LPS)-induced Kupffer cell activation with subsequent reduction in hepatic leukocyte-endothelial cell interaction, thereby achieving protection against microcirculatory perfusion failure and hepatic dysfunction. To further clarify the underlying mechanisms, rG-CSF treated liver cells were tested for the LPS-induced gene expression of cytokine-induced neutrophil chemoattractant (CINC) and intercellular adhesion molecule-1 (ICAM-1) as potential chemotactic and leukocyte-recruiting factors and for the gene expression of inducible nitric oxide synthase (NOS II) as potential modulator of leukocyte adherence.
  
  
  METHODS
  Using a collagenase, DNAse/pronase digestion technique, hepatic parenchymal and nonparenchymal cell fractions were obtained from livers of in vivo rG-CSF pretreated Sprague-Dawley rats 2 h after LPS exposure. mRNA transcripts were assessed using northern blot analysis.
  
  
  RESULTS
  In control livers only ICAM-1 mRNA was found constitutively expressed in hepatic nonparenchymal cells. rG-CSF per se did not affect NOS II, CINC, or ICAM-1 expression in hepatic liver cells, while LPS induced a marked expression of NOS II, CINC, and ICAM-1 in nonparenchymal cells and, to a lesser extent, in hepatocytes. Administration of rG-CSF prior to LPS exposure tended to increase NOS II, CINC, and ICAM-1 mRNA transcripts in hepatocytes. In nonparenchymal cells, however, NOS II and CINC were found reduced in rG-CSF pretreated animals upon LPS exposure.
  
  
  CONCLUSIONS
  The present data show a strikingly different cell type specific pattern of inflammatory response genes in rG-CSF-modulated hepatic endotoxemia. Reduced expression of NOS II, in particular of CINC, in the nonparenchymal cell fraction may contribute to the reduced leukocyte adherence and thus attenuation of cell-dependent tissue injury in rG-CSF pretreated endotoxemic animals.
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000235:genetics*; D002630:Chemotactic Factors / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D019446:Endotoxemia / Q000235:genetics / Q000473:pathology*; D004926:Escherichia coli; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins