title: Activation of counter-regulatory mechanisms in a rat renal acute rejection model.
abstract: BACKGROUND
  Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation.
  
  
  RESULTS
  We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family.
  
  
  CONCLUSIONS
  Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.
authors.affiliation: Experimentelle Nephrologie, Medizinische Klinik und Poliklinik D, Universitätsklinikum Münster, Germany. edemir@uni-muenster.de
authors.forename: Bayram
authors.initials: B
authors.lastname: Edemir
authors.forename: Sunil M
authors.initials: SM
authors.lastname: Kurian
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.forename: Detlef
authors.initials: D
authors.lastname: Lang
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.forename: Gert
authors.initials: G
authors.lastname: Gabriëls
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Salomon
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schlatter
mesh_terms: D000208:Acute Disease; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D018925:Chemokines / Q000235:genetics; D003167:Complement Activation / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II; D005819:Genetic Markers; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology*; D007372:Interferons / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D018925:Chemokines; D016207:Cytokines; D005819:Genetic Markers; D007372:Interferons