Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-1-21
pubmed:abstractText
Interleukin-1? (IL-1?) is critical for inflammation and control of infection. The production of IL-1? depends on expression of pro-IL-1? and inflammasome component induced by inflammatory stimuli, followed by assembly of inflammasome to generate caspase-1 for cleavage of pro-IL-1?. Here we show that tumor suppressor death-associated protein kinase (DAPK) deficiency impaired IL-1? production in macrophages. Generation of tumor necrosis factor-? in macrophages, in contrast, was not affected by DAPK knockout. Two tiers of defects in IL-1? generation were found in DAPK-deficient macrophages: decreased pro-IL-1? induction by some stimuli and reduced caspase-1 activation by all inflammatory stimuli examined. With a normal NLRP3 induction in DAPK-deficient macrophages, the diminished caspase-1 generation is attributed to impaired inflammasome assembly. There is a direct binding of DAPK to NLRP3, suggesting an involvement of DAPK in inflammasome formation. We further illustrated that the formation of NLRP3 inflammasome in situ induced by inflammatory signals was impaired by DAPK deficiency. Taken together, our results identify DAPK as a molecule required for full production of IL-1? and functional assembly of the NLRP3 inflammasome. In addition, DAPK knockout reduced uric acid crystal-triggered peritonitis, suggesting that DAPK may serve as a target in the treatment of IL-1?-associated autoinflammatory diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
960-70
pubmed:meshHeading
pubmed-meshheading:21041719-Animals, pubmed-meshheading:21041719-Apoptosis Regulatory Proteins, pubmed-meshheading:21041719-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:21041719-Carrier Proteins, pubmed-meshheading:21041719-Caspase 1, pubmed-meshheading:21041719-Cell Line, pubmed-meshheading:21041719-Cytoskeletal Proteins, pubmed-meshheading:21041719-HEK293 Cells, pubmed-meshheading:21041719-Humans, pubmed-meshheading:21041719-Immunoblotting, pubmed-meshheading:21041719-Inflammation, pubmed-meshheading:21041719-Interleukin-1beta, pubmed-meshheading:21041719-Macrophages, pubmed-meshheading:21041719-Mice, pubmed-meshheading:21041719-Mice, Inbred C57BL, pubmed-meshheading:21041719-Mice, Knockout, pubmed-meshheading:21041719-Mutation, pubmed-meshheading:21041719-Protein Binding, pubmed-meshheading:21041719-RNA Interference, pubmed-meshheading:21041719-Transfection, pubmed-meshheading:21041719-Tumor Suppressor Proteins
pubmed:year
2011
pubmed:articleTitle
Tumor suppressor death-associated protein kinase is required for full IL-1? production.
pubmed:affiliation
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't