| First Author | Summersgill H | Year | 2014 |
| Journal | Cell Death Dis | Volume | 5 |
| Pages | e1040 | PubMed ID | 24481454 |
| Mgi Jnum | J:305688 | Mgi Id | MGI:6705260 |
| Doi | 10.1038/cddis.2013.547 | Citation | Summersgill H, et al. (2014) Zinc depletion regulates the processing and secretion of IL-1beta. Cell Death Dis 5:e1040 |
| abstractText | Sterile inflammation contributes to many common and serious human diseases. The pro-inflammatory cytokine interleukin-1beta (IL-1beta) drives sterile inflammatory responses and is thus a very attractive therapeutic target. Activation of IL-1beta in sterile diseases commonly requires an intracellular multi-protein complex called the NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome. A number of disease-associated danger molecules are known to activate the NLRP3 inflammasome. We show here that depletion of zinc from macrophages, a paradigm for zinc deficiency, also activates the NLRP3 inflammasome and induces IL-1beta secretion. Our data suggest that zinc depletion damages the integrity of lysosomes and that this event is important for NLRP3 activation. These data provide new mechanistic insight to how zinc deficiency contributes to inflammation and further unravel the mechanisms of NLRP3 inflammasome activation. |
