Inhibition of MD-1 expression by immunosuppressants or antisense oligodeoxynucleotides on skin allograft survival in mice.
OBJECTIVE
The aim of this study was to investigate the effects of inhibition of MD-1 expression using nonspecific immunosuppressants and specific antisense oligodeoxynucleotides (AS-ODNs) treatment on skin allograft survival in mice.


METHODS
C57BL/6 to Balb/c skin allograft model was used in all groups, followed by Cyclosporine (CsA), Tacrolimus (FK506), Mycophenolate Mofetil (MMF), and Sirolimus (SRL) intraperitaneally, as well as AS-ODNs intravenously. Recipients were humanely killed at 11 days after transplantation. MD-1 expression was determined using flow cytometric analysis (FACS). AlamarBlue was used to evaluate proliferation. And serum levels of interleukin (IL)-2 and IL-10 were detected using enzyme-linked immunosorbent assay (ELISA).


RESULTS
Compared with saline controls, the mean survival times (MST) of skin allografts in all of the immunosuppressants and AS-ODNs treated groups were significantly prolonged (P < .05). CsA, MMF, and AS-ODNs inhibited MD-1 expression and lymphocyte proliferation, as well as decreased serum level of IL-2 and increased that of IL-10; FK506, treatment showed all the effects mentioned above but up-regulated the IL-10 level; SRL had no significant influence on either MD-1 expression or IL-2 and IL-10 level, although it equally suppressed the proliferation (P < .05 vs controls). The negative correlation between MD-1 expression and lymphocyte proliferation or IL-2 level was significant, as was the positive correlation between it and IL-10 level (P < .01).


CONCLUSIONS
CsA, FK506, MMF, and AS-ODNs can efficiently inhibit MD-1 expression. The effects of the immunosuppressants are seemingly associated with the down-regulation of the IL-2 serum level. MD-1 was theorized to play an important role in rejection promotion, although the precise relationship between it and allograft survival still remains ambiguous.
Zhang
X
X
Key Laboratory of Organ Transplantation, Ministry of Education, PR China.
Chen
B C
BC
Xiang
F L
FL
Chang
S
S
Zhou
H M
HM
Du
D F
DF
Yuan
J
J
Chen
Z K
ZK
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D005434:Flow Cytometry; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D007376:Interleukin-2; C113553:Ly86 protein, mouse; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D016753:Interleukin-10