Mesenchymal stem cell transplantation inhibited high salt-induced activation of the NLRP3 inflammasome in the renal medulla in Dahl S rats

Abstract

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.