کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4303158 | 1288472 | 2010 | 6 صفحه PDF | دانلود رایگان |
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-α (TNF-α), and interferon-γ (IFN-γ) in the graft. Our results suggest that IL-2 targeting using RNA interference approach may be of potential interest in organ transplantation.
Journal: Journal of Surgical Research - Volume 159, Issue 1, March 2010, Pages 582–587