Thioredoxin-1 attenuates early graft loss after intraportal islet transplantation in mice.
OBJECTIVE
Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.


METHODS
Intraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control and a TRX group. In addition, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.


RESULTS
The changes in blood glucose levels were significantly lower in the TRX group compared with the TRX-Tg donor and control groups (p<0.01). Glucose tolerance and the residual graft mass were considerably better in the TRX group. TRX significantly suppressed the serum levels of interleukin-1β (p<0.05), although neither anti-apoptotic nor anti-chemotactic effects were observed. Notably, no increase in the 8-hydroxy-2'-deoxyguanosine level was observed after islet infusion, irrespective of TRX administration.


CONCLUSIONS
The present study demonstrates that overexpression of TRX on the islet grafts is not sufficient to improve engraftment. In contrast, TRX administration to the recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1β. However, TRX alone appears to be insufficient to completely prevent early graft loss after islet transplantation. We therefore propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation.
Division of Advanced Surgical Science and Technology, Tohoku University, Sendai, Japan.
Kengo
K
Asami
Akiko
A
Inagaki
Takehiro
T
Imura
Satoshi
S
Sekiguchi
Keisei
K
Fujimori
Hiroshi
H
Masutani
Junji
J
Yodoi
Susumu
S
Satomi
Noriaki
N
Ohuchi
Masafumi
M
Goto
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D007275:Injections, Intravenous; D053583:Interleukin-1beta / Q000097:blood; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D011169:Portal Vein; D013311:Streptozocin; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D001786:Blood Glucose; D053583:Interleukin-1beta; C515559:Txn1 protein, mouse; D013879:Thioredoxins; D013311:Streptozocin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine