@article{ebd63dda145144169dff90b522012719,
title = "Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation",
abstract = "NLRP3-inflammasome-driven inflammation is involved in the pathogenesis of a variety of diseases. Identification of endogenous inflammasome activators is essential for the development of new anti-inflammatory treatment strategies. Here, we identified that apolipoprotein C3 (ApoC3) activates the NLRP3 inflammasome in human monocytes by inducing an alternative NLRP3 inflammasome via caspase-8 and dimerization of Toll-like receptors 2 and 4. Alternative inflammasome activation in human monocytes is mediated by the Toll-like receptor adapter protein SCIMP. This triggers Lyn/Syk-dependent calcium entry and the production of reactive oxygen species, leading to activation of caspase-8. In humanized mouse models, ApoC3 activated human monocytes in vivo to impede endothelial regeneration and promote kidney injury in an NLRP3- and caspase-8-dependent manner. These data provide new insights into the regulation of the NLRP3 inflammasome and the pathophysiological role of triglyceride-rich lipoproteins containing ApoC3. Targeting ApoC3 might prevent organ damage and provide an anti-inflammatory treatment for vascular and kidney diseases.",
keywords = "OF-FUNCTION MUTATIONS, NLRP3 INFLAMMASOME, ENDOTHELIAL DYSFUNCTION, PATTERN-RECOGNITION, CELL-DEATH, APOC-III, PROTEIN, RECEPTOR, ADAPTER, CIII",
author = "Stephen Zewinger and Jochen Reiser and Vera Jankowski and Dalia Alansary and Eunsil Hahm and Sarah Triem and Mira Klug and Schunk, {Stefan J.} and David Schmit and Rafael Kramann and Christina Koerbel and Emmanuel Ampofo and Laschke, {Matthias W.} and Simina-Ramona Selejan and Anna Paschen and Tobias Herter and Susanne Schuster and Guenther Silbernagel and Martina Sester and Urban Sester and Gunter Assmann and Robert Bals and Gerhard Kostner and Willi Jahnen-Dechent and Menger, {Michael D.} and Lucia Rohrer and Winfried Maerz and Michael Boehm and Joachim Jankowski and Manfred Kopf and Eicke Latz and Niemeyer, {Barbara A.} and Danilo Fliser and Ulrich Laufs and Thimoteus Speer",
note = "Funding Information: This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB/ TRR 219), Else-Kr{\"o}ener Fresenius Foundation, Deutsche Nierenstiftung and European Uremic Toxin Work Group of the ERA-EDTA. This study was supported by funding from the European Community{\textquoteright}s program {\textquoteleft}European Regional Development Fund Interreg{\textquoteright} to {\textquoteleft}EURIPIDS{\textquoteright} and the Deutsche Forschungsgemeinschaft (SFB894 A2, SFB1027 C4 and SFB TRR 219). Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = jan,
doi = "10.1038/s41590-019-0548-1",
language = "English",
volume = "21",
pages = "30--41",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "1",
}