Knockdown of interleukin-2 by shRNA-mediated RNA interference prolongs liver allograft survival.
Interleukin-2 (IL-2) plays a central role in T-cell activation, expansion, and homeostasis. The failure of IL-2 biosynthesis may play a critical role in tolerance induction. We tested the effect of IL-2 blockade by short hairpin RNA (shRNA) on regulating acute rejection in rat liver transplantation. To this end, we successfully designed and selected an effective interference plasmid, pIL-2B. The IL-2 mRNA expression level in the pIL-2B group was one-fifth of that in the no transfection group. Lewis to BN orthotopic liver transplant model was used to explore the effect of knockdown IL-2 by shRNA in vivo. Recipients treated with pIL-2-shRNA survived longer (median survival time of 16 d range 7-21 d) than those with empty vector (11; range 5-13) or saline (9; range 5-13) (P<0.05), and was inferior to those with CsA (24; range 13-36, P<0.05). The IL-2-shRNA attenuated acute rejection with decreased apoptosis of hepatocytes and reduced cytokine production of IL-2, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the graft. Our results suggest that IL-2 targeting using RNA interference approach may be of potential interest in organ transplantation.
Chen
Yong
Y
Chongqing Key Laboratory of Hepatobliliary Surgery and Department of Hepatobliliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.
Yan
Tao
T
Shi
Liu-jun
LJ
Liu
Zuojin
Z
Liang
Shao-yong
SY
Luan
Xiao-feng
XF
Long
Fei-wu
FW
Chen
Jie
J
Peng
Yong
Y
Yan
Lü-nan
LN
Gong
Jian-ping
JP
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D016207:Cytokines / Q000097:blood; D055785:Gene Knockdown Techniques; D006084:Graft Rejection; D006085:Graft Survival; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016031:Liver Transplantation; D008969:Molecular Sequence Data; D010957:Plasmids; D034622:RNA Interference; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D016207:Cytokines; D007376:Interleukin-2