RESUMO
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.
Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Interleucina-2/metabolismo , Transplante de Fígado , Animais , Apoptose , Sequência de Bases , Citocinas/sangue , Técnicas de Silenciamento de Genes , Interleucina-2/genética , Dados de Sequência Molecular , Plasmídeos , Interferência de RNA , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante HomólogoRESUMO
Understanding the spatial patterns of human-wildlife conflict is essential to inform management decisions to encourage coexistence, but it is constrained by the lack of spatially-explicit data. We collected spatially-implicit data of human-wildlife conflicts from 2009-2015 around Daxueshan Nature Reserve, Yunnan, China, and investigated the patterns and drivers of these conflicts. A questionnaire was also designed to capture local resident attitudes toward insurance-based compensation for the losses caused by targeted wildlife. We found that the Asiatic black bear (Ursus thibetanus) was the most conflict-prone animal around the reserve, followed by the rhesus macaque (Macaca mulatta) and Southeast Asian sambar (Cervus equinus). Conflicts were unevenly distributed among seasons, villages, and communities, with several grids identified as conflict hotspots. Poisson models revealed that human-bear conflicts were negatively related to distance to the reserve and proportion of forest, but positively correlated to the proportion of cropland. Binomial models showed that communities affected by crop depredation were positively correlated with the proportion of cropland and negatively correlated with distance to the reserve, whereas communities affected by livestock depredation were negatively correlated with the proportion of cropland. The insurance-based scheme has compensated over 90% of losses, to the satisfaction of 90.6% of respondents. Our results suggest that human-bear conflict could be potentially reduced by eliminating food crops near the reserve boundary and livestock grazing at conflict hotspots. In addition, the insurance-based scheme could be replicated at a broader scale with improvement in loss assessment.