title: Microarray-based gene expression profiles of allograft rejection and immunosuppression in the rat heart transplantation model.
abstract: BACKGROUND
  Gene expression profiling has the potential to produce new insights into complex biologic systems. To test the value of complement DNA arrays in identifying pathways involved in organ transplant rejection, we examined the gene expression profiles of rat heart allografts from recipients treated with or without immunosuppression to prevent acute allograft rejection.
  
  
  METHODS
  Heterotopic heart transplantation was performed using ACI or Lewis donors and Lewis recipients. Recipients were treated with tacrolimus (Tac) or cyclosporine (CsA) at the equivalent effective doses, and graft hearts were harvested on days 3, 5, and 7. A commercial microarray was used to measure gene expression levels of 588 genes in day 5 grafts. Selected genes were analyzed by reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  The expression levels of 118 genes were perturbed in the untreated allograft in comparison with the isograft control, of which 77 genes were categorized as candidate genes for Tac- or CsA-mediated immunosuppression or both, and 41 as genes associated with other pathways. Among the 77 candidate genes, 55 genes shared the same response to suppression by both drugs, including inducible nitric oxide synthase, interferon-gamma, and interferon regulatory factor 1. Drug-specific effects were observed in 22 genes: Fourteen genes were exclusively reversed by Tac and eight by CsA.
  
  
  CONCLUSIONS
  Gene expression profiling reveals a large variety of genes affected during acute rejection, indicating that multiple metabolic pathways, including immune and nonimmune responses, are involved in the local graft rejection events. The differences and similarities of the gene expression profiles relative to the two immunosuppressants may provide more detailed therapeutic approaches for optimal immunosuppression.
authors.affiliation: Fujisawa Research Institute of America, Northwestern University/Evanston Research Park, Evanston, Illinois 60201, USA.
authors.forename: Laurie M
authors.initials: LM
authors.lastname: Erickson
authors.forename: Fan
authors.initials: F
authors.lastname: Pan
authors.forename: Aaron
authors.initials: A
authors.lastname: Ebbs
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hongsi
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D015870:Gene Expression / Q000502:physiology*; D006084:Graft Rejection / Q000235:genetics*; D016027:Heart Transplantation; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus