Prolonged survival time of allografts by the oral administration of RDP58 linked to the cholera toxin B subunit.
Oral administration, which has been identified as a tool for boosting physiological immunoregulatory mechanisms in an antigen-specific manner, is a more convenient way than classical parenteral injection methods. RDP58 is derived from specific regions of class-I MHC molecules and is known to have immunomodulatory effects after intraperitoneal injection or intravenous administration. To determine whether the oral administration of RDP58 conjugated to the cholera toxin B subunit (CTB) can better induce peripheral tolerance than the use of traditional methods, we used various feeding regimens and methods of administration using equivalent doses of antigen during rat kidney transplantation. The results showed that RDP58-GC/CTB treatment increased the activity of Haem oxygenase-1 (HO-1) in vivo and significantly improved the survival and histopathology of allograft kidney tissue relative to the oral administration of RDP58 alone. These results suggest that the administration of RDP58 linked to CTB outweighs the benefits of oral administration of RDP58 alone for prolonging the survival time of kidney transplantation. This study supports the potential therapeutic use of oral administration of RDP58 linked to CTB as a platform molecule in the treatment of allograft rejection.
Urological Research Institute of PLA, Southwest Hospital, Third Military Medical University, Chongqing, 400036, China.
Xuesong
X
Yu
Bo
B
Song
Chibing
C
Huang
Ya
Y
Xiao
Mingqi
M
Fang
Jiayu
J
Feng
Pingxian
P
Wang
Genfu
G
Zhang
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D010455:Peptides / Q000008:administration & dosage*; D061166:Peripheral Tolerance; D051381:Rats; D011914:Rats, Inbred BN
D015395:Histocompatibility Antigens Class I; D010455:Peptides; C092373:allotrap; D002772:Cholera Toxin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1