| First Author | Wali JA | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 11 | Pages | e113128 |
| PubMed ID | 25405767 | Mgi Jnum | J:225299 |
| Mgi Id | MGI:5692363 | Doi | 10.1371/journal.pone.0113128 |
| Citation | Wali JA, et al. (2014) Activation of the NLRP3 inflammasome complex is not required for stress-induced death of pancreatic islets. PLoS One 9(11):e113128 |
| abstractText | 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. |
