Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4.
Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4.
复制标题
DOI：
10.1038/ki.2011.140
复制
发表时间：
2011-09
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然白细胞在缺血性急性肾损伤（阿基）期间浸润肾脏并释放白细胞介素6（IL 6），但其激活机制尚不清楚。在这里，我们测试了白细胞上的Toll样受体4（TLR 4）是否通过与缺血性肾损伤后肾细胞释放的高迁移率族蛋白B1（HMGB 1）相互作用来介导这种激活。我们使用C3 H/HeJ和C57 BL/10 ScNJ品系的TLR 4（-/-）小鼠及其各自的TLR 4（+/+）野生型对应物构建了辐射诱导的骨髓嵌合体，并在缺血损伤后4小时对其进行了研究。从TLR 4（+/+）小鼠获得的白细胞浸润TLR 4（−/−）小鼠的肾脏，TLR 4（−/−）白细胞浸润TLR 4（+/+）小鼠的肾脏，但在每种情况下都几乎不引起功能性肾损伤。最大缺血性阿基需要来自TLR 4（+/+）小鼠的放射敏感性白细胞和放射抗性肾实质和内皮细胞。只有TLR 4（−/−）白细胞在体内产生IL 6，并在体外响应HMGB 1。因此，在浸润损伤的肾后，当白细胞的TLR 4受体与由损伤的肾细胞释放的HMGB 1相互作用时，白细胞产生IL 6。这强调了TLR 4在缺血性阿基发病机制中的重要性。
Although leukocytes infiltrate the kidney during ischemic acute kidney injury (AKI) and release interleukin 6 (IL6), their mechanism of activation is unknown. Here, we tested whether Toll-like receptor 4 (TLR4) on leukocytes mediated this activation by interacting with high-mobility group protein B1 (HMGB1) released by renal cells as a consequence of ischemic kidney injury. We constructed radiation-induced bone marrow chimeras using C3H/HeJ and C57BL/10ScNJ strains of TLR4 (−/−) mice and their respective TLR4 (+/+) wild-type counterparts and studied them at 4 h after an ischemic insult. Leukocytes adopted from TLR4 (+/+) mice infiltrated the kidneys of TLR4 (−/−) mice, and TLR4 (−/−) leukocytes infiltrated the kidneys of TLR4 (+/+) mice but caused little functional renal impairment in each case. Maximal ischemic AKI required both radiosensitive leukocytes and radioresistant renal parenchymal and endothelial cells from TLR4 (+/+) mice. Only TLR4 (−/−) leukocytes produced IL6 in vivo and in response to HMGB1 in vitro. Thus, following infiltration of the injured kidney, leukocytes produce IL6 when their TLR4 receptors interact with HMGB1 released by injured renal cells. This underscores the importance of TLR4 in the pathogenesis of ischemic AKI.
登录
查看更多内容
影响因子：
8.7
作者：
Beutler B
通讯作者：
Beutler B
影响因子：
13.6
作者：
Kielar, ML;John, R;Lu, CY
通讯作者：
Lu, CY
影响因子：
19.6
作者：
Chen, Jianlin;John, Reji;Richardson, James A.;Shelton, John M.;Zhou, Xin J.;Wang, Yanxia;Wu, Qing Qing;Hartono, John R.;Winterberg, Pamela D.;Lu, Christopher Y.
通讯作者：
Lu, Christopher Y.
影响因子：
5.4
作者：
Kalis, C;Kanzler, B;Freudenberg, MA
通讯作者：
Freudenberg, MA
影响因子：
15.1
作者：
Eisener-Dorman, Amy F.;Lawrence, David A.;Bolivar, Valerie J.
通讯作者：
Bolivar, Valerie J.