Autoinflammatory disease regulated by IL-1B (inflammasomopathies) and NFKB
Mechanisms of autoinflammatory disease regulated by IL-1β (inflammasomopathies) and NF-κB. The NLRP3 protein interacts with ASC and caspase-1 to form a complex termed the inflammasome, which is a macromolecular complex that processes IL-1β into its active form. Mutations (denoted by asterisks) in proteins that affect the function of this complex such as pyrin, PSTPIP1, mevalonate kinase (MK), and NLRP7 thus represent extrinsic inflammasomopathies. Mutations in NLRP3 clearly activate the molecule; however, the precise mechanism by which pyrin and PSTPIP1 mutations regulate inflammasome activity has not been determined. As NLRP7 is a negative regulator of IL-1β production, these mutations are likely to inactivate the protein, and it has been shown that MK mutations are also loss of function, although the pathway that leads from these mutations to Rac1/PI3K/PKB activation is not yet formally described. Preliminary data from our laboratory suggest that mutations in the IL-1 receptor antagonist (IL-1Ra) cause another extrinsic inflammasomopathy. For NF-κB activation disorders, NOD2 could become activated by mutations that may relieve autorepression of the molecule; however, there are also persuasive data showing that mutations inactivate the protein from tolerizing the host to the bacterial cell wall component muramyl dipeptide (MDP). NLRP12 is a negative regulator of NF-κB, and thus a proinflammatory disease would be caused by what appear to be loss-of-function mutations. Abbreviations used: CPPD, calcium pyrophosphate dihydrate; Aβ, amyloid-β; ROS, reactive oxygen species; PKB, protein kinase B.

Publication
Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease. () Seth L. Masters, et al. Annu Rev Immunol. ;27:621-668. Figure: F2.Organism | Group | Word | Match | Source | NCBI Symbol | NCBI ID |
---|---|---|---|---|---|---|
Homo sapiens | Primates | IL-1B | IL1B | ncbigene_symbol | IL1B | 3553 |
Homo sapiens | Primates | NF-KB | NF-KB | ncbigene_synonym | NFKB1 | 4790 |
Homo sapiens | Primates | MDP | MDP | ncbigene_synonym | DPEP1 | 1800 |
Homo sapiens | Primates | AB, | AB | ncbigene_synonym | APP | 351 |
Homo sapiens | Primates | AB, | AB | ncbigene_synonym | SUCLA2 | 8803 |
Homo sapiens | Primates | PSTPIP1 | PSTPIP1 | ncbigene_symbol | PSTPIP1 | 9051 |
Homo sapiens | Primates | NLRP3 | NLRP3 | ncbigene_symbol | NLRP3 | 114548 |
Homo sapiens | Primates | ASC | ASC | ncbigene_synonym | STS | 412 |
Homo sapiens | Primates | ASC | ASC | ncbigene_synonym | PYCARD | 29108 |
Homo sapiens | Primates | RIP2 | RIP2 | ncbigene_synonym | RIPK2 | 8767 |
Homo sapiens | Primates | RIP2 | RIP2 | ncbigene_synonym | ARHGEF28 | 64283 |
Homo sapiens | Primates | NLRP12 | NLRP12 | ncbigene_symbol | NLRP12 | 91662 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP1 | 834 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP2 | 835 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP4 | 837 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP5 | 838 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP6 | 839 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP8 | 841 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP9 | 842 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP10 | 843 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP12 | 100506742 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP14 | 23581 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP3 | 836 |
Homo sapiens | Primates | caspase | CASPASE | famplex_relations | CASP7 | 840 |
Homo sapiens | Primates | NLRP7* | NLRP7 | ncbigene_symbol | NLRP7 | 199713 |
Homo sapiens | Primates | PKB | PKB | ncbigene_synonym | AKT1 | 207 |
Homo sapiens | Primates | PKB | PKB | ncbigene_synonym | PTK2B | 2185 |
Homo sapiens | Primates | proll-18 | PROL2 | ncbigene_synonym | PNRC1 | 10957 |
Homo sapiens | Primates | proll-18 | PROL1 | ncbigene_synonym | OPRPN | 58503 |
Homo sapiens | Primates | proll-18 | PROL3 | ncbigene_synonym | SMR3B | 10879 |
Homo sapiens | Primates | proll-18 | PROL5 | ncbigene_synonym | SMR3A | 26952 |
Homo sapiens | Primates | proll-18 | PROL4 | ncbigene_synonym | PRR4 | 11272 |
Homo sapiens | Primates | IL-1Ra | IL-1RA | ncbigene_synonym | IL1RN | 3557 |
Homo sapiens | Primates | IL-1Ra | IL-1RA | ncbigene_synonym | IL6R | 3570 |
Homo sapiens | Primates | IL-16 | IL16 | ncbigene_symbol | IL16 | 3603 |
Homo sapiens | Primates | p50 | P50 | ncbigene_synonym | CD40 | 958 |
Homo sapiens | Primates | p50 | P50 | ncbigene_synonym | ARHGEF7 | 8874 |
Homo sapiens | Primates | p50 | P50 | ncbigene_synonym | ASCC1 | 51008 |
Homo sapiens | Primates | p50 | P50 | ncbigene_synonym | H3P40 | 115482723 |
Homo sapiens | Primates | P65 | P65 | ncbigene_synonym | RELA | 5970 |
Homo sapiens | Primates | P65 | P65 | ncbigene_synonym | SYT1 | 6857 |
Homo sapiens | Primates | P65 | P65 | ncbigene_synonym | GORASP1 | 64689 |
Homo sapiens | Primates | P65 | P65 | ncbigene_synonym | WNK1 | 65125 |
Word | Match | MeSH | Name | ChEBI |
---|---|---|---|---|
cholesterol | Cholesterol | mesh:D002784 | cholesterol | chebi:16113 |
silica | Silicon Dioxide | mesh:D012822 | silicon dioxide | chebi:30563 |
Uric acid | NA | mesh:D014527 |
Disease mentions
Word | Match | MeSH | Name | DOID |
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