Nanomaterial induced inflammasome activation (Homo sapiens)

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Description

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.

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Ontology Terms

 

Bibliography

  1. Farrera C, Fadeel B; ''It takes two to tango: Understanding the interactions between engineered nanomaterials and the immune system.''; Eur J Pharm Biopharm, 2015 PubMed
  2. Bhattacharya K, Andón FT, El-Sayed R, Fadeel B; ''Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation.''; Adv Drug Deliv Rev, 2013 PubMed

History

View all...
CompareRevisionActionTimeUserComment
94756view15:35, 5 October 2017Mkutmonfix unconnected lines
92318view08:51, 20 May 2017EgonwOntology Term : 'nanomaterial response pathway' added !
92313view08:47, 20 May 2017EgonwOntology Term : 'xenobiotic metabolic pathway' added !
91312view19:08, 26 January 2017KhanspersModified title
89364view06:25, 8 September 2016TorresandonModified description
89363view06:13, 8 September 2016TorresandonPAMPs
89362view06:07, 8 September 2016TorresandonUpdate TLR receptor and necessary stimuli for the activation of the pathway
89305view13:23, 31 August 2016EgonwOntology Term : 'regulatory pathway' added !
89304view13:23, 31 August 2016EgonwOntology Term : 'macrophage' added !
89303view13:22, 31 August 2016EgonwOntology Term : 'PW:0001018' removed !
89302view13:22, 31 August 2016EgonwOntology Term : 'innate immune response pathway' added !
89301view13:21, 31 August 2016EgonwOntology Term : 'immune system disease pathway' added !
89286view13:09, 30 August 2016TorresandonAdd references
89285view13:06, 30 August 2016TorresandonAdd references
89284view12:13, 30 August 2016TorresandonNew pathway

External references

Datanodes

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NameTypeDatabase referenceComment
ASC
Caspase-1 (Fragment)ProteinH0YEC7 (Uniprot-TrEMBL)
Caspase-1ProteinB4DVD8 (Uniprot-TrEMBL)
Cathepsin BProteinE9PCB3 (Uniprot-TrEMBL)
IL1BGeneProductENSG00000125538 (Ensembl)
IL1BProteinP01584 (Uniprot-TrEMBL)
NADPH oxidase 1ProteinA6NGA6 (Uniprot-TrEMBL)
NFKB1GeneProductNFKB1 (HGNC)
NLRP3ProteinA0A024R5Q0 (Uniprot-TrEMBL)
PAMPs
PotassiumMetaboliteHMDB00586 (HMDB)
ROS productionMetaboliteCHEBI:26523 (ChEBI)
TLR4GeneProductENSG00000136869 (Ensembl)
pro-IL-1bProteinP01584 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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