Matches in SemOpenAlex for { <https://semopenalex.org/work/W2328686711> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W2328686711 endingPage "135" @default.
- W2328686711 startingPage "135.1" @default.
- W2328686711 abstract "<h3>Background</h3> Rheumatoid arthritis (RA) is characterized by proliferation of synovial fibroblasts (FLS), activation of these cells by synovial macrophages (Mϕ), and production of pro-inflammatory proteins. As genetic backgrounds do not completely explain the etiology of RA, a growing attention has focused on potential epigenetic contributions to inflammation. <h3>Objectives</h3> Here we examined the role of the closely related epigenetic regulatory proteins sirtuin 1 (Sirt1) and sirtuin 2 (Sirt2), class III histone deacetylases, in the inflammatory activation of RA FLS and human macrophages. <h3>Methods</h3> Sirt1 and Sirt2 mRNA and protein expression was measured in RA FLS following stimulation with IL-1β and TNF-α. RA-FLS production of IL-6, IL-8, MMP-1 and MMP-3 mRNA and protein expression in response to IL-1β, in the absence or presence of specific inhibitors for Sirt1 and Sirt2, was measured by quantitative PCR (qPCR) and ELISA. The expression of 84 genes regulated by IL-1β in RA FLS were analyzed by qPCR array in the presence or absence of Sirt2-specific inhibitor. Monocytes obtained from healthy volunteers were differentiated into either M1 or M2 macrophages with human recombinant IFN-γ or IL-10 for 7 days. Macrophage production of IL-6 and IL-8 in response to LPS stimulation in the absence or presence of Sirt inhibitors was assessed by ELISA. <h3>Results</h3> The expression of Sirt1 was enhanced following RA FLS IL-1β stimulation, while Sirt2 expression was significantly reduced (p<0.05). Pharmacological inhibition of Sirt2, but not Sirt1, significantly reduced RA FLS expression of IL-6, IL-8, and MMP-3 mRNA, in response to IL-1β stimulation (p<0.05), an effect mimicked at the protein level. qPCR array analysis demonstrated that mRNA expression of 18 of 84 genes induced by IL-1β in RA FLS (n=3) were significantly reduced by 50% or more in the presence of Sirt2 inhibitor. Furthermore Sirt2 inhibitor reduced LPS-induced levels of IL-8 in IFN-γ–but not IL-10–differentiated macrophages. <h3>Conclusions</h3> Our studies identify Sirt2 as a novel epigenetic regulator of inflammatory activation of macrophages and RA FLS. <h3>Disclosure of Interest</h3> E. Mohammadi: None declared, C. Angiolilli: None declared, P. Kabala: None declared, P. Tak Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, D. Baeten: None declared, F. Husseini Shirazi: None declared, K. Reedquist: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4012" @default.
- W2328686711 created "2016-06-24" @default.
- W2328686711 creator A5000834093 @default.
- W2328686711 creator A5005557422 @default.
- W2328686711 creator A5016618633 @default.
- W2328686711 creator A5046625022 @default.
- W2328686711 creator A5049606459 @default.
- W2328686711 creator A5061179734 @default.
- W2328686711 creator A5007277650 @default.
- W2328686711 date "2014-06-01" @default.
- W2328686711 modified "2023-09-26" @default.
- W2328686711 title "OP0192 Sirtuin Deacetylase 2 Inhibition Suppresses Inflammatory Activation of Rheumatoid Arthritis Fibroblast-Like Synoviocytes and IFN-Γ–Differentiated Macrophages" @default.
- W2328686711 doi "https://doi.org/10.1136/annrheumdis-2014-eular.4012" @default.
- W2328686711 hasPublicationYear "2014" @default.
- W2328686711 type Work @default.
- W2328686711 sameAs 2328686711 @default.
- W2328686711 citedByCount "0" @default.
- W2328686711 crossrefType "journal-article" @default.
- W2328686711 hasAuthorship W2328686711A5000834093 @default.
- W2328686711 hasAuthorship W2328686711A5005557422 @default.
- W2328686711 hasAuthorship W2328686711A5007277650 @default.
- W2328686711 hasAuthorship W2328686711A5016618633 @default.
- W2328686711 hasAuthorship W2328686711A5046625022 @default.
- W2328686711 hasAuthorship W2328686711A5049606459 @default.
- W2328686711 hasAuthorship W2328686711A5061179734 @default.
- W2328686711 hasConcept C104317684 @default.
- W2328686711 hasConcept C119157956 @default.
- W2328686711 hasConcept C127561419 @default.
- W2328686711 hasConcept C199848840 @default.
- W2328686711 hasConcept C203014093 @default.
- W2328686711 hasConcept C2776536020 @default.
- W2328686711 hasConcept C2776745794 @default.
- W2328686711 hasConcept C2776914184 @default.
- W2328686711 hasConcept C2777077863 @default.
- W2328686711 hasConcept C2777575956 @default.
- W2328686711 hasConcept C2778305200 @default.
- W2328686711 hasConcept C2780561631 @default.
- W2328686711 hasConcept C41091548 @default.
- W2328686711 hasConcept C502942594 @default.
- W2328686711 hasConcept C55493867 @default.
- W2328686711 hasConcept C64927066 @default.
- W2328686711 hasConcept C71924100 @default.
- W2328686711 hasConcept C86803240 @default.
- W2328686711 hasConceptScore W2328686711C104317684 @default.
- W2328686711 hasConceptScore W2328686711C119157956 @default.
- W2328686711 hasConceptScore W2328686711C127561419 @default.
- W2328686711 hasConceptScore W2328686711C199848840 @default.
- W2328686711 hasConceptScore W2328686711C203014093 @default.
- W2328686711 hasConceptScore W2328686711C2776536020 @default.
- W2328686711 hasConceptScore W2328686711C2776745794 @default.
- W2328686711 hasConceptScore W2328686711C2776914184 @default.
- W2328686711 hasConceptScore W2328686711C2777077863 @default.
- W2328686711 hasConceptScore W2328686711C2777575956 @default.
- W2328686711 hasConceptScore W2328686711C2778305200 @default.
- W2328686711 hasConceptScore W2328686711C2780561631 @default.
- W2328686711 hasConceptScore W2328686711C41091548 @default.
- W2328686711 hasConceptScore W2328686711C502942594 @default.
- W2328686711 hasConceptScore W2328686711C55493867 @default.
- W2328686711 hasConceptScore W2328686711C64927066 @default.
- W2328686711 hasConceptScore W2328686711C71924100 @default.
- W2328686711 hasConceptScore W2328686711C86803240 @default.
- W2328686711 hasIssue "Suppl 2" @default.
- W2328686711 hasLocation W23286867111 @default.
- W2328686711 hasOpenAccess W2328686711 @default.
- W2328686711 hasPrimaryLocation W23286867111 @default.
- W2328686711 hasRelatedWork W1854362516 @default.
- W2328686711 hasRelatedWork W1989666486 @default.
- W2328686711 hasRelatedWork W2032537932 @default.
- W2328686711 hasRelatedWork W2072808244 @default.
- W2328686711 hasRelatedWork W2076339051 @default.
- W2328686711 hasRelatedWork W2277544136 @default.
- W2328686711 hasRelatedWork W2328686711 @default.
- W2328686711 hasRelatedWork W2912920575 @default.
- W2328686711 hasRelatedWork W3170748956 @default.
- W2328686711 hasRelatedWork W3213993055 @default.
- W2328686711 hasVolume "73" @default.
- W2328686711 isParatext "false" @default.
- W2328686711 isRetracted "false" @default.
- W2328686711 magId "2328686711" @default.
- W2328686711 workType "article" @default.