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

Authors

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

Cited In

Organism

Homo sapiens

Communities

Adverse Outcome Pathways Nanomaterials Pathways

Annotations

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

Cell Type Ontology: macrophage

Participants

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

References

  1. Bhattacharya K, Andón FT, El-Sayed R, Fadeel B. Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation. Adv Drug Deliv Rev. 2013 Dec;65(15):2087–97. PubMed Europe PMC Scholia
  2. Farrera C, Fadeel B. It takes two to tango: Understanding the interactions between engineered nanomaterials and the immune system. Eur J Pharm Biopharm. 2015 Sep;95(Pt A):3–12. PubMed Europe PMC Scholia