Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT-1/IRF-1 pathway during tolerance induction.
This study aimed to define the molecular mechanism during induction of spontaneous liver transplant tolerance using microarrays and to focus on molecular pathways associated with tolerance by meta-analysis with published studies. The differences in the early immune response between PVG to DA liver transplant recipients that are spontaneously tolerant (TOL) and PVG to Lewis liver transplants that reject (REJ) were examined. Spleens from TOL and REJ on days 1 and 3 were compared by 2 color microarray. Forty-six of 199 genes differentially expressed between TOL and REJ had an immunological function. More immune genes were increased in TOL vs. REJ on day 1, including STAT-1, IRF-1 and complement C3. Differential expression of selected genes was confirmed by quantitative RT-PCR. The results were compared to two published high-throughput studies of rat liver transplant tolerance and showed that C3 was increased in all three models, while STAT-1 and IRF-1 were increased in two models. The early increases in immune genes in TOL confirmed previous reports of an active early immune response in TOL. In conclusion, the increase in STAT-1, IRF-1 and complement component C3 in several models of liver transplant tolerance suggests that the STAT-1/IRF-1 apoptotic pathway and C3 may be involved in the tolerogenic mechanism.
Cordoba
Shaun P
SP
AW Morrow Liver Immunobiology Laboratory, Centenary Institute, UNSW Sydney, Australia.
Wang
Chuanmin
C
Williams
Rohan
R
Li
Jian
J
Smit
Lynn
L
Sharland
Alexandra
A
Allen
Richard
R
McCaughan
Geoffrey
G
Bishop
Alex
A
D000818:Animals; D003176:Complement C3 / Q000235:genetics*; D006084:Graft Rejection; D006085:Graft Survival; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics*; D013154:Spleen / Q000502:physiology; D023001:Transplantation Tolerance / Q000502:physiology*
D003176:Complement C3; D050856:Interferon Regulatory Factor-1; D050794:STAT1 Transcription Factor; D012313:RNA