Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection.
BACKGROUND
Long-term survival of a graft requires inhibition of host immune effectors, but protective responses emanating from the graft might be equally important. Expression of the "protective" genes A20, heme-oxygenase-1 (HO-1), and Bcl-xL in rodent allo and xenografts correlates with long-term survival. Little is known of the pattern of expression of such protective genes and the implication thereof in clinical transplantation.


METHODS
We analyzed, by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, expression of A20, HO-1, and Bcl-xL in 31 renal allograft biopsies from patients with suspected rejection.


RESULTS
A20 is not expressed in nonrejecting (NR) grafts. Its expression is increased in grafts undergoing acute and chronic rejection (AR and CR) but is weaker in CR. HO-1 is not expressed in NR grafts; it is up-regulated in AR but not CR. Bcl-xL is detected in all biopsies with decreased levels in CR. Expression of A20, HO-1, and Bcl-xL localizes mainly to endothelial, smooth muscle, and infiltrating mononuclear cells.


CONCLUSIONS
This data demonstrate that A20 and HO-1 are up-regulated in response to immune injury inferred by AR. Given the antiapoptotic and antiinflammatory functions of these genes, we hypothesize that their expression survives to limit graft injury by maintaining cell viability and controlling inflammation. Their reduced expression in CR as compared with AR represents either inadequate response to injury or a sequelae of prior injury that jeopardizes further tissue response to immune attack.
Avihingsanon
Yingyos
Y
Division of Immunology, Department of Medicine, Immunobiology Research Center, Harvard Medical School, Boston, MA 02215, USA.
Ma
Naili
N
Csizmadia
Eva
E
Wang
Candace
C
Pavlakis
Martha
M
Giraldo
Mauricio
M
Strom
Terry B
TB
Soares
Miguel P
MP
Ferran
Christiane
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins; D006084:Graft Rejection / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D016030:Kidney Transplantation; D008565:Membrane Proteins; D008875:Middle Aged; D009687:Nuclear Proteins; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3