期刊
EXPERIMENTAL CELL RESEARCH
卷 341, 期 1, 页码 42-53出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2016.01.014
关键词
Peritoneal mesothelial cells; Mitophagy/autophagy; Resveratrol; ROS; NLRP3
资金
- National Natural Science Foundation of China [81200555]
It has been suggested that continuous exposure of peritoneal mesothelial cells (PMCs) to high glucose containing peritoneal dialysis (PD) solutions may result in peritoneal inflammatory injury and impairment of local peritoneal host defence. Here, we investigated the effect of glucose-based PD solutions on mitochondrial reactive oxygen species (ROS) and nod-like receptor 3 (NLRP3) inflammasome activation in human PMCs (HPMCs). Exposure of HPMCs to high glucose-based PD solutions resulted in ROS production, which can trigger NLRP3 activation, leading to IL-1 beta secretion. Additionally, resveratrol (RSV) treatment induced mitophagy/autophagy via adenosine monophosphate-activated protein kinase (AMPK) activation. Increased mitochondrial ROS concentrations and IL-1 beta upregulation were confirmed following inhibition (siRNA against Beclin1 and ATG5 or autophagy inhibitor 3MA), but not induction (RSV), of mitophagy/autophagy. Furthermore, we observed that ATG5 and Beclin1 downregulation sensitised cells to IL-I beta release induced by MSU or nigericin, which is an NLRP3 inflammasome activator. RSV treatment attenuated this effect. Taken together, this study may provide a potential therapeutic strategy for peritoneal inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS. (C) 2016 Elsevier Inc. All rights reserved.
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