Inhibition of UII/UTR system relieves acute inflammation of liver through preventing activation of NF-κB pathway in ALF mice.
Inhibition of UII/UTR system relieves acute inflammation of liver through preventing activation of NF-κB pathway in ALF mice.
复制标题
DOI：
10.1371/journal.pone.0064895
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang YY
中科院分区：
文献类型：
--
作者：
Liang DY;Liu LM;Ye CG;Zhao L;Yu FP;Gao DY;Wang YY;Yang ZW;Wang YY
尾加压素II（UII）通过其特异性高亲和力UT受体（UTR）参与免疫炎症性疾病。UII/UTR的表达增强最近被证明在急性肝衰竭（ALF）的肝脏。在这里，我们分析了UII/UTR表达和ALF在脂多糖（LPS）/D-半乳糖胺（GalN）攻击小鼠之间的关系。此后，我们研究了UII/UTR系统的抑制所产生的影响，一个特殊的UTR拮抗剂，并参与ALF的潜在分子机制。将Urantide施用至用LPS/GalN处理的小鼠。在有或没有Urantide预处理的致死性ALF中，评估UII/UTR的表达，促炎细胞因子包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1β）和干扰素-γ（IFN-γ）的释放，以及核因子κB（NF-κB）信号通路的激活。我们发现，LPS/GalN攻击的小鼠表现出高死亡率和显著的肝脏炎症浸润和细胞凋亡以及UII/UTR表达的显著增加。Urantide预处理对UII/UTR表达下调后的肝损伤具有保护作用。急性肝损伤与UII/UTR表达密切相关。此外，铀酰肽可抑制LPS/GalN诱导的小鼠TNF-α、IL-1β和IFN-γ等促炎细胞因子的升高及NF-κB信号通路的激活。因此，我们认为UII/UTR系统在LPS/GalN诱导的ALF中起作用。Urantide对急性炎症性肝损伤的保护作用部分是通过抑制促炎细胞因子的释放和激活NF-κB通路实现的。
Urotensin II (UII) is implicated in immune inflammatory diseases through its specific high-affinity UT receptor (UTR). Enhanced expression of UII/UTR was recently demonstrated in the liver with acute liver failure (ALF). Here, we analysed the relationship between UII/UTR expression and ALF in lipopolysaccharide (LPS)/D-galactosamine (GalN)-challenged mice. Thereafter, we investigated the effects produced by the inhibition of UII/UTR system using urantide, a special antagonist of UTR, and the potential molecular mechanisms involved in ALF. Urantide was administered to mice treated with LPS/GalN. Expression of UII/UTR, releases of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interferon-γ (IFN-γ), and activation of nuclear factor κB (NF-κB) signaling pathway were assessed in the lethal ALF with or without urantide pretreatment. We found that LPS/GalN-challenged mice showed high mortality and marked hepatic inflammatory infiltration and cell apoptosis as well as a significant increase of UII/UTR expression. Urantide pretreatment protected against the injury in liver following downregulation of UII/UTR expression. A close relationship between the acutely flamed hepatic injury and UII/UTR expression was observed. In addition, urantide prevented the increases of proinflammatory cytokines such as TNF-α, IL-1β and IFN-γ, and activation of NF-κB signaling pathway induced by LPS/GalN in mice. Thus, we conclude that UII/UTR system plays a role in LPS/GalN-induced ALF. Urantide has a protective effect on the acutely inflamed injury of liver in part through preventing releases of proinflammatory cytokines and activation of NF-κB pathway.
登录
查看更多内容
Pim-3 可预防 D-半乳糖胺 (D-GalN) 致敏大鼠的肝衰竭
DOI：
10.1111/j.1365-2362.2009.02235.x
发表时间：
2010-02-01
影响因子：
5.5
作者：
Liu, L. -M.;Zhang, J. -X.;Luo, J.
通讯作者：
Luo, J.
影响因子：
37.8
作者：
Ng, LL;Loke, I;Davies, JE
通讯作者：
Davies, JE
影响因子：
1.5
作者：
Chai, San Bao;Li, Xue Min;Tang, Chao Shu
通讯作者：
Tang, Chao Shu
影响因子：
3.6
作者：
Johns, DG;Ao, ZH;Douglas, SA
通讯作者：
Douglas, SA
影响因子：
3.5
作者：
Coulouarn, Y;Jégou, S;Lihrmann, I
通讯作者：
Lihrmann, I