Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts.
Acute rejection and graft arteriopathy in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by several cytokines and adhesion molecules. Nuclear factor-kappa B (NFkappaB) is critical in the transcription of multiple genes involved in inflammation and cell proliferation. To test the hypothesis that NFkappaB decoy can attenuate acute rejection and arteriopathy, we performed single intraluminal delivery of NFkappaB decoy into murine cardiac allografts using a hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE)-liposome method. No decoy or scrambled decoy transfer was performed for control. Hearts were heterotopically transplanted from BALB/c to C3H/He mice (major mismatch group) and from DBA/2 to B10.D2 mice (minor mismatch group). Nontreated or scrambled decoy transfected allografts of the major mismatch group were acutely rejected, while NFkappaB decoy prolonged their survival. While severe cell infiltration and intimal thickening with enhancement of inflammatory factors were observed in untreated or scrambled decoy-treated allografts of minor mismatch group at day 28, NFkappaB decoy attenuated these changes. We conclude that NFkappaB is critically involved in the development of acute as well as chronic rejection of the transplanted hearts. NFkappaB decoy attenuates both acute rejection and graft arteriopathy by blocking the activation of several genes.
Suzuki
J
J
Department of Internal Medicine I, Shinshu University School of Medicine, Nagano, Japan.
Morishita
R
R
Amano
J
J
Kaneda
Y
Y
Isobe
M
M
D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics*; D005822:Genetic Vectors / Q000008:administration & dosage; D006084:Graft Rejection / Q000235:genetics; D016027:Heart Transplantation / Q000276:immunology*; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics* / Q000502:physiology; D018108:Respirovirus / Q000235:genetics; D014162:Transfection / Q000379:methods*; D014184:Transplantation, Homologous
D008081:Liposomes; D016328:NF-kappa B