PMID- 11965035 OWN - NLM STAT- MEDLINE DCOM- 20020508 LR - 20190713 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 73 IP - 7 DP - 2002 Apr 15 TI - Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection. PG - 1079-85 AB - 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. FAU - Avihingsanon, Yingyos AU - Avihingsanon Y AD - Division of Immunology, Department of Medicine, Immunobiology Research Center, Harvard Medical School, Boston, MA 02215, USA. FAU - Ma, Naili AU - Ma N FAU - Csizmadia, Eva AU - Csizmadia E FAU - Wang, Candace AU - Wang C FAU - Pavlakis, Martha AU - Pavlakis M FAU - Giraldo, Mauricio AU - Giraldo M FAU - Strom, Terry B AU - Strom TB FAU - Soares, Miguel P AU - Soares MP FAU - Ferran, Christiane AU - Ferran C LA - eng GR - 1 UO1 AI46134/AI/NIAID NIH HHS/United States GR - 5 R01 HL57791-04/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (BCL2L1 protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-X Protein) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 3.4.19.12 (TNFAIP3 protein, human) RN - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Child MH - Child, Preschool MH - DNA-Binding Proteins MH - Graft Rejection/*metabolism MH - Heme Oxygenase (Decyclizing)/analysis/*genetics MH - Heme Oxygenase-1 MH - Humans MH - Immunohistochemistry MH - Intracellular Signaling Peptides and Proteins MH - *Kidney Transplantation MH - Membrane Proteins MH - Middle Aged MH - Nuclear Proteins MH - Proteins/analysis/*genetics MH - Proto-Oncogene Proteins c-bcl-2/analysis/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transplantation, Homologous MH - Tumor Necrosis Factor alpha-Induced Protein 3 MH - bcl-X Protein EDAT- 2002/04/20 10:00 MHDA- 2002/05/09 10:01 CRDT- 2002/04/20 10:00 PHST- 2002/04/20 10:00 [pubmed] PHST- 2002/05/09 10:01 [medline] PHST- 2002/04/20 10:00 [entrez] AID - 10.1097/00007890-200204150-00011 [doi] PST - ppublish SO - Transplantation. 2002 Apr 15;73(7):1079-85. doi: 10.1097/00007890-200204150-00011.