Nanomaterial induced inflammasome activation (Homo sapiens)

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Lysosome Inflammasome Nanomaterial-Associated Molecular Patterns IL1B Cathepsin B pro-IL-1b IL1B NFKB1 ROS production TLR4 Potassium Caspase-1 (Fragment) NADPH oxidase 1 PAMPs NLRP3 Caspase-1 ASC Potassium Name: Nanomaterial induced inflammasome activation Organism: Homo sapiens


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

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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...
RevisionActionTimeUserComment
94756view 08:35, 5 October 2017Mkutmonfix unconnected lines
92318view 01:51, 20 May 2017EgonwOntology Term : 'nanomaterial response pathway' added !
92313view 01:47, 20 May 2017EgonwOntology Term : 'xenobiotic metabolic pathway' added !
91312view 12:08, 26 January 2017KhanspersModified title
89364view 23:25, 7 September 2016TorresandonModified description
89363view 23:13, 7 September 2016TorresandonPAMPs
89362view 23:07, 7 September 2016TorresandonUpdate TLR receptor and necessary stimuli for the activation of the pathway
89305view 06:23, 31 August 2016EgonwOntology Term : 'regulatory pathway' added !
89304view 06:23, 31 August 2016EgonwOntology Term : 'macrophage' added !
89303view 06:22, 31 August 2016EgonwOntology Term : 'PW:0001018' removed !
89302view 06:22, 31 August 2016EgonwOntology Term : 'innate immune response pathway' added !
89301view 06:21, 31 August 2016EgonwOntology Term : 'immune system disease pathway' added !
89286view 06:09, 30 August 2016TorresandonAdd references
89285view 06:06, 30 August 2016TorresandonAdd references
89284view 05:13, 30 August 2016TorresandonNew pathway

External references

DataNodes

View all...
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

<cite>No annotated interactions</cite>