Nanomaterial-induced inflammasome activation (WP3890)

This is a schematic diagram illustrating putative pathways for NAMP (nanomaterial-associated molecular patters)-induced NLRP3 inflammasome activation. Pathogen-associated molecular patterns (PAMPs) eg. lipopolysaccharides (LPS) are recognized by Toll-like receptors (TLRs) on the cell membrane, which leads to NF-κB activation and upregulation of pro-interleukin (IL)-1β and NLRP3 expression. High aspect radio nanomaterials (i.e. long multiwalled carbon nanotubes) are thought to trigger “frustrated phagocytosis” in macrophages, leading to NADPH oxidase activation, reactive oxygen species (ROS) generation and inflammasome activation. Smaller nanomaterials (i.e. short carbon nanotubes or silver nanoparticles of 28 nm), on the other hand, could be phagocytosed and once inside the cell induce lysosomal damage leading to release of cathepsins which cause mitochondrial damage and ROS production. In both cases, interaction of phagocytes with NAMPs induces an overproduction of ROS which results in assembly of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD), and pro-caspase-1 into the multimeric inflammasome complex, resulting in activation of caspase-1, and release of mature IL-1β, a key pro-inflammatory mediator.
last edited


Torresandon, Egonw, Khanspers, Mkutmon, MaintBot, AlexanderPico, and Eweitz

Cited In


Homo sapiens


Adverse Outcome Pathways Nanomaterials Pathways


Pathway Ontology: xenobiotic metabolic pathway regulatory pathway nanomaterial response pathway innate immune response pathway

Cell Type Ontology: macrophage


Label Type Compact Identifier
IL1B Rna ensembl:ENSG00000125538
NLRP3 Protein uniprot:A0A024R5Q0
CTSB Protein uniprot:E9PCB3
pro-IL-1b Protein uniprot:P01584
IL1B Protein uniprot:P01584
NFKB1 GeneProduct hgnc.symbol:NFKB1
ROS Metabolite chebi:26523
TLR4 GeneProduct ensembl:ENSG00000136869
Potassium Metabolite hmdb:HMDB0000586
CASP1 Protein uniprot:H0YEC7
pro-CASP1 Protein uniprot:B4DVD8
ASC GeneProduct ensembl:ENSG00000103490
NOX1 Protein uniprot:A6NGA6
Potassium Metabolite hmdb:HMDB0000586


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