Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation

Autor: Thimoteus Speer, Anna Paschen, Joachim Jankowski, David Schmit, Lucia Rohrer, Eicke Latz, Sarah Triem, Willi Jahnen-Dechent, Jochen Reiser, Vera Jankowski, Barbara A. Niemeyer, Gunter Aßmann, Gerhard M. Kostner, Michael D. Menger, Christina Körbel, Danilo Fliser, Stephen Zewinger, Susanne Schuster, Rafael Kramann, Michael Böhm, Simina-Ramona Selejan, Manfred Kopf, Winfried März, Ulrich Laufs, Dalia Alansary, Mira Klug, Eunsil Hahm, Tobias Herter, Günther Silbernagel, Robert Bals, Martina Sester, Urban Sester, Emmanuel Ampofo, Stefan J Schunk, Matthias W. Laschke
Přispěvatelé: Internal Medicine, Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
immunology [Acute Kidney Injury]
immunology [NLR Family
Pyrin Domain-Containing 3 Protein]
Inflammasomes
metabolism [Toll-Like Receptor 4]
PROTEIN
APOC-III
ADAPTER
Monocytes
Inflammasome
NLRP3 INFLAMMASOME
Mice
0302 clinical medicine
immunology [Inflammation]
immunology [Apolipoprotein C-III]
Mice
Inbred NOD
NOD-like receptors
OF-FUNCTION MUTATIONS
Immunology and Allergy
metabolism [Reactive Oxygen Species]
Receptor
Mice
Knockout
Caspase 8
integumentary system
Chemistry
Signal transducing adaptor protein
TLR2 protein
human
Acute Kidney Injury
Cell biology
SCIMP protein
human
TLR4 protein
human
APOC3 protein
human
Kidney Diseases
medicine.symptom
metabolism [Caspase 8]
medicine.drug
Programmed cell death
metabolism [Toll-Like Receptor 2]
Immunology
Inflammation
Cell Line
03 medical and health sciences
genetics [Inflammation]
immunology [Monocytes]
immunology [Kidney Diseases]
LYN
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
NLRP3 protein
human
Animals
Humans
ddc:610
Monocytes and macrophages
Adaptor Proteins
Signal Transducing
Apolipoprotein C-III
RECEPTOR
HEK 293 cells
genetics [Apolipoprotein C-III]
Membrane Proteins
pathology [Kidney Diseases]
Toll-Like Receptor 2
immunology [Inflammasomes]
pathology [Acute Kidney Injury]
Mice
Inbred C57BL
Toll-Like Receptor 4
Disease Models
Animal
030104 developmental biology
HEK293 Cells
CELL-DEATH
Humanized mouse
ENDOTHELIAL DYSFUNCTION
PATTERN-RECOGNITION
Reactive Oxygen Species
CIII
030215 immunology
Zdroj: Nature Immunology, 21(1), 30-+. Nature Publishing Group
Nature immunology 21(1), 30-41 (2019). doi:10.1038/s41590-019-0548-1
Nature Immunology, 21(1), 30-41. Nature Publishing Group
ISSN: 1529-2908
DOI: 10.1038/s41590-019-0548-1
Popis: 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.
Databáze: OpenAIRE
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