Activation of the NLRP3 inflammasome complex is not required for stress-induced death of pancreatic islets
- Author(s)
- Wali, JA; Gurzov, EN; Fynch, S; Elkerbout, L; Kay, TW; Masters, SL; Thomas, HE;
- Details
- Publication Year 2014,Volume 9,Issue #11,Page e113128
- Journal Title
- PLoS One
- Publication Type
- Journal Article
- Abstract
- Loss of pancreatic beta cells is a feature of type-2 diabetes. High glucose concentrations induce endoplasmic reticulum (ER) and oxidative stress-mediated apoptosis of islet cells in vitro. ER stress, oxidative stress and high glucose concentrations may also activate the NLRP3 inflammasome leading to interleukin (IL)-1beta production and caspase-1 dependent pyroptosis. However, whether IL-1beta or intrinsic NLRP3 inflammasome activation contributes to beta cell death is controversial. This possibility was examined in mouse islets. Exposure of islets lacking functional NLRP3 or caspase-1 to H2O2, rotenone or thapsigargin induced similar cell death as in wild-type islets. This suggests that oxidative or ER stress do not cause inflammasome-mediated cell death. Similarly, deficiency of NLRP3 inflammasome components did not provide any protection from glucose, ribose or gluco-lipotoxicity. Finally, genetic activation of NLRP3 specifically in beta cells did not increase IL-1beta production or cell death, even in response to glucolipotoxicity. Overall, our results show that glucose-, ER stress- or oxidative stress-induced cell death in islet cells is not dependent on intrinsic activation of the NLRP3 inflammasome.
- Publisher
- PLOS
- Research Division(s)
- Inflammation
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0113128
- Open Access at Publisher's Site
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- Refer to copyright notice on published article.
Creation Date: 2015-03-12 03:59:03
Last Modified: 2015-03-16 09:28:52