Circulating monocytes accelerate acute liver failure by IL-6 secretion in monkey.
Circulating monocytes accelerate acute liver failure by IL-6 secretion in monkey.
复制标题
循环单核细胞分泌IL-6加速猴急性肝衰竭
DOI：
10.1111/jcmm.13673
复制
发表时间：
2018-09
影响因子：
5.3
通讯作者：
Bu H
中科院分区：
文献类型：
--
作者：
Guo G;Zhu Y;Wu Z;Ji H;Lu X;Zhou Y;Li Y;Cao X;Lu Y;Talbot P;Liao J;Shi Y;Bu H
急性肝衰竭（ALF）与高死亡率相关，并且对潜在病理生理学的了解不足导致迄今为止缺乏有效的治疗方法。在这里，我们利用鹅膏毒素诱导的恒河猴 ALF 模型，全景揭示了导致 ALF 发生的细胞和分子事件。受到毒素攻击的猴子经历了典型的 ALF 过程，包括严重肝损伤、全身炎症和最终死亡。在 ALF 的整个过程中，适应性免疫并未受到明显干扰。对血清因子和细胞因子的系统检查表明，IL-6 的增加最快、最剧烈。有趣的是，我们发现 IL-6 主要由循环单核细胞产生。此外，消除小鼠单核细胞来源的 IL-6 可减少化学注射后的肝损伤和全身炎症。我们的研究结果揭示了循环单核细胞在启动和加速 ALF 中的关键作用，表明 ALF 临床治疗的潜在治疗靶点。
Acute liver failure (ALF) is associated with high mortality, and a poor understanding of the underlying pathophysiology has resulted in a lack of effective treatments so far. Here, using an amatoxin‐induced rhesus monkey model of ALF, we panoramically revealed the cellular and molecular events that lead to the development of ALF. The challenged monkeys with toxins underwent a typical course of ALF including severe hepatic injury, systemic inflammation and eventual death. Adaptive immune was not noticeably disturbed throughout the progress of ALF. A systematic examination of serum factors and cytokines revealed that IL‐6 increase was the most rapid and drastic. Interestingly, we found that IL‐6 was mainly produced by circulating monocytes. Furthermore, ablation of monocyte‐derived IL‐6 in mice decreased liver injury and systemic inflammation following chemical injection. Our findings reveal a critical role of circulating monocytes in initiating and accelerating ALF, indicating a potential therapeutic target in clinical treatment for ALF.
登录
查看更多内容
肝组织工程：从移植到实验室定制的基于细胞的肝脏定向疗法。
影响因子：
5.3
作者：
Fiegel HC;Kaufmann PM;Bruns H;Kluth D;Horch RE;Vacanti JP;Kneser U
通讯作者：
Kneser U
影响因子：
29.4
作者：
Liu, ZX;Govindarajan, S;Kaplowitz, N
通讯作者：
Kaplowitz, N
影响因子：
3.6
作者：
Bélanger, M;Butterworth, RF
通讯作者：
Butterworth, RF
影响因子：
13.5
作者：
Rolando, N;Wade, J;Williams, R
通讯作者：
Williams, R
影响因子：
25.7
作者：
Bernardi, Mauro;Moreau, Richard;Arroyo, Vicente
通讯作者：
Arroyo, Vicente