Zhu Qing, Li Xiao-Xue, Wang Weili, Hu Junping, Li Pin-Lan, Conley Sabena, Li Ningjun
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia.
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
Am J Physiol Renal Physiol. 2016 Apr 1;310(7):F621-F627. doi: 10.1152/ajprenal.00344.2015. Epub 2016 Jan 13.
Inflammasomes activate caspase-1 to produce interleukin (IL)-1β. Activation of the NLRP3 inflammasome is involved in various renal pathological conditions. It remains unknown whether the NLRP3 inflammasome activation participates in the abnormal renal response to high-salt (HS) diet in Dahl salt-sensitive (S) rats. In addition, our lab recently showed that transplantation of mesenchymal stem cells (MSCs) attenuated HS-induced inflammation in the renal medulla in Dahl S rat. However, it is unclear whether the anti-inflammatory action of MSCs is associated with inhibition of the NLRP3 inflammasome. The present study determined the response of the NLRP3 inflammasome to HS intake and the effect of MSC transplantation on the NLRP3 inflammasome in the renal medulla in Dahl S rats. Immunostaining showed that the inflammasome components NLRP3, ASC, and caspase-1 were mainly present in distal tubules and collecting ducts. Interestingly, the renal medullary levels of these inflammasome components were remarkably increased after a HS diet in Dahl S rats, while remaining unchanged in normal rats. This HS-induced activation of the NLRP3 inflammasome was significantly blocked by MSC transplantation into the renal medulla in Dahl S rats. Furthermore, infusion of a caspase-1 inhibitor into the renal medulla significantly attenuated HS-induced hypertension in Dahl S rats. These data suggest that HS-induced activation of the NLRP3 inflammasome may contribute to renal medullary dysfunction in Dahl S rats and that inhibition of inflammasome activation may be one of the mechanisms for the anti-inflammatory and anti-hypertensive effects of stem cells in the renal medulla in Dahl S rats.
炎性小体激活半胱天冬酶 -1以产生白细胞介素（IL）-1β。NLRP3炎性小体的激活参与多种肾脏病理状况。NLRP3炎性小体激活是否参与 Dahl 盐敏感（S）大鼠对高盐（HS）饮食的异常肾脏反应仍不清楚。此外，我们实验室最近表明，间充质干细胞（MSC）移植可减轻 Dahl S 大鼠肾髓质中 HS 诱导的炎症。然而，尚不清楚 MSC 的抗炎作用是否与抑制 NLRP3 炎性小体有关。本研究确定了 NLRP3 炎性小体对 HS 摄入的反应以及 MSC 移植对 Dahl S 大鼠肾髓质中 NLRP3 炎性小体的影响。免疫染色显示，炎性小体成分 NLRP3、ASC 和半胱天冬酶 -1 主要存在于远端小管和集合管中。有趣的是，Dahl S 大鼠在 HS 饮食后，这些炎性小体成分的肾髓质水平显著升高，而正常大鼠中则保持不变。Dahl S 大鼠肾髓质内 MSC 移植可显著阻断这种 HS 诱导的 NLRP3 炎性小体激活。此外，向肾髓质内注入半胱天冬酶 -1 抑制剂可显著减轻 Dahl S 大鼠中 HS 诱导的高血压。这些数据表明，HS 诱导的 NLRP3 炎性小体激活可能导致 Dahl S 大鼠肾髓质功能障碍，并且抑制炎性小体激活可能是干细胞对 Dahl S 大鼠肾髓质产生抗炎和抗高血压作用的机制之一。
