A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1.
A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1.
复制标题
一种新型环状螺旋 B 肽在通过 Jak-2/STAT3/SOCS1 改善急性肾移植排斥过程中抑制树突状细胞成熟。
DOI：
10.1038/cddis.2015.338
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发表时间：
2015-11-26
影响因子：
9
通讯作者：
Zhu T
中科院分区：
文献类型：
--
作者：
Yang C;Zhang Y;Wang J;Li L;Wang L;Hu M;Xu M;Long Y;Rong R;Zhu T
我们最近合成了一种新的抗蛋白水解的环状螺旋B肽（CHBP），具有良好的肾脏保护作用。树突状细胞（Dendritic cells，DCs）在急性排斥反应（Acute Rejection，AR）中起激活作用。因此，本研究旨在研究CHBP对大鼠肾移植模型中DC的影响。从雄性刘易斯大鼠中收获左肾，然后移植到有或没有CHBP处理的雄性Wistar大鼠中。移植后连续5次CHBP治疗剂量显著改善了AR，降低了移植肾的组织学损伤、细胞凋亡和CD 4+和CD 8 + T细胞浸润。CHBP降低血清中IFN-γ和IL-1β水平，但升高IL-4和IL-10水平。CHBP处理的移植肾中成熟DC数量明显减少。此外，CHBP与DCs体外孵育可降低DCs培养上清中TNF-α、IFN-γ、IL-1β和IL-12的水平，增加IL-10的表达。CHBP通过Jak-2/STAT 3信号转导增加SOCS 1表达，从而抑制TLR激活诱导的DC成熟。结论：CHBP通过Jak-2/STAT 3/SOCS 1信号通路抑制DCs的成熟，从而抑制移植肾AR，提示CHBP可能是一种潜在的治疗肾AR的药物。
We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. Dendritic cells (DCs) play an activation role in acute rejection (AR). Thus, the present study was designed to investigate the effects of CHBP on DCs in a rat renal transplantation model. The left kidney was harvested from male Lewis rats and then transplanted into male Wistar rats with or without CHBP treatment. Five successive treatment doses of CHBP after transplantation significantly ameliorated AR with lower histological injury, apoptosis and CD4+ and CD8+ T-cell infiltration in renal allografts. CHBP reduced IFN-γ and IL-1β levels but increased IL-4 and IL-10 levels in the serum. The number of mature DCs was significantly decreased in renal allografts treated with CHBP. In addition, incubating DCs with CHBP in vitro led to reduction in TNF-α, IFN-γ, IL-1β and IL-12 levels and increase of IL-10 expression at the protein level in the supernatant. Mechanistically, CHBP inhibited TLR activation-induced DC maturation by increasing SOCS1 expression through Jak-2/STAT3 signaling. In conclusion, CHBP suppresses renal allograft AR by inhibiting the maturation of DCs via Jak-2/STAT3/SOCS1 signaling, suggesting that CHBP may be an potential therapeutic drug for treating renal AR.