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dc.contributor.authorDavaro, Facundo
dc.contributor.authorForde, Sorcha D.
dc.contributor.authorGarfield, Mark
dc.contributor.authorJiang, Zhaozhao
dc.contributor.authorHalmen, Kristen A.
dc.contributor.authorTamburro, Nelsy DePaula
dc.contributor.authorKurt-Jones, Evelyn A.
dc.contributor.authorFitzgerald, Katherine A.
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorWang, Donghai
dc.date2022-08-11T08:09:08.000
dc.date.accessioned2022-08-23T16:19:02Z
dc.date.available2022-08-23T16:19:02Z
dc.date.issued2014-06-06
dc.date.submitted2014-11-26
dc.identifier.citationJ Biol Chem. 2014 Jun 6;289(23):16214-22. doi: 10.1074/jbc.M114.571505. Epub 2014 Apr 30. <a href="http://dx.doi.org/10.1074/jbc.M114.571505">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M114.571505
dc.identifier.pmid24790079
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34952
dc.description.abstractMultiple clinical trials have shown that the 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors known as statins have anti-inflammatory effects. However, the underlying molecular mechanism remains unclear. The proinflammatory cytokine interleukin-1beta (IL-1beta) is synthesized as a non-active precursor. The 31-kDa pro-IL-1beta is processed into the 17-kDa active form by caspase-1-activating inflammasomes. Here, we report a novel signaling pathway induced by statins, which leads to processing of pro-IL-1beta into an intermediate 28-kDa form. This statin-induced IL-1beta processing is independent of caspase-1- activating inflammasomes. The 28-kDa form of IL-1beta cannot activate interleukin-1 receptor-1 (IL1R1) to signal inflammatory responses. Instead, it interferes with mature IL-1beta signaling through IL-1R1 and therefore may dampen inflammatory responses initiated by mature IL-1beta. These results may provide new clues to explain the anti-inflammatory effects of statins.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24790079&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M114.571505
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectHydroxymethylglutaryl-CoA Reductase Inhibitors
dc.subjectInterleukin-1beta
dc.subjectMacrophages
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectSignal Transduction
dc.subjectBiochemistry
dc.subjectImmunity
dc.subjectImmunology and Infectious Disease
dc.subjectImmunology of Infectious Disease
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.title3-Hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin)-induced 28-kDa interleukin-1beta interferes with mature IL-1beta signaling
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume289
dc.source.issue23
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/174
dc.identifier.contextkey6399371
html.description.abstract<p>Multiple clinical trials have shown that the 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors known as statins have anti-inflammatory effects. However, the underlying molecular mechanism remains unclear. The proinflammatory cytokine interleukin-1beta (IL-1beta) is synthesized as a non-active precursor. The 31-kDa pro-IL-1beta is processed into the 17-kDa active form by caspase-1-activating inflammasomes. Here, we report a novel signaling pathway induced by statins, which leads to processing of pro-IL-1beta into an intermediate 28-kDa form. This statin-induced IL-1beta processing is independent of caspase-1- activating inflammasomes. The 28-kDa form of IL-1beta cannot activate interleukin-1 receptor-1 (IL1R1) to signal inflammatory responses. Instead, it interferes with mature IL-1beta signaling through IL-1R1 and therefore may dampen inflammatory responses initiated by mature IL-1beta. These results may provide new clues to explain the anti-inflammatory effects of statins.</p>
dc.identifier.submissionpathinfdis_pp/174
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages16214-22


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