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.
Autoinflammatory disease regulated by IL-1B (inflammasomopathies) and NFKB

Publication

Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease. () Seth L. Masters, et al. Annu Rev Immunol. ;27:621-668. Figure: F2.

Gene mentions


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

Chemical mentions

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