UM
Jmjd3-mediated epigenetic regulation of inflammatory cytokine gene expression in serum amyloid A-stimulated macrophages
Yan Q.2; Sun L.2; Zhu Z.2; Wang L.2; Li S.2; Ye R.D.2
2014
Source PublicationCellular Signalling
ISSN18733913 08986568
Volume26Issue:9Pages:1783-1791
AbstractSerum amyloid A (SAA), a major acute-phase protein, has potent cytokine-like activities in isolated phagocytes and synovial fibroblasts. SAA-induced proinflammatory cytokine gene expression requires transcription factors such as NF-κB; however, the associated epigenetic regulatory mechanism remains unclear. Here we report that Jmjd3, a histone H3 lysine 27 (H3K27) demethylase, is highly inducible in SAA-stimulated macrophages and plays an important role in the induction of inflammatory cytokine genes. SAA-induced Jmjd3 expression leads to reduced H3K27 trimethylation. Silencing of Jmjd3 expression significantly inhibited SAA-induced expression of proinflammatory cytokines including IL-23p19, G-CSF and TREM-1, along with up-regulation of H3K27 trimethylation levels on their promoters. Depletion of Jmjd3 expression also attenuated the release of proinflammatory cytokine genes in a peritonitis model and ameliorated neutrophilia in SAA-stimulated mice. Finally, we observed that Jmjd3 is essential for SAA-enhanced macrophage foam cell formation by oxidized LDL. Taken together, these results illustrate a Jmjd3-dependent epigenetic regulatory mechanism for proinflammatory cytokine gene expression in SAA-stimulate macrophages. This mechanism may be subject to therapeutic intervention for sterile inflammation and atherosclerosis. © 2014 Elsevier Inc.
KeywordHistone demethylase Jmjd3 Macrophages Serum amyloid A Sterile inflammation
DOI10.1016/j.cellsig.2014.03.025
URLView the original
Language英語
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Cited Times [WOS]:46   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Illinois College of Medicine
2.Shanghai Jiao Tong University
Recommended Citation
GB/T 7714
Yan Q.,Sun L.,Zhu Z.,et al. Jmjd3-mediated epigenetic regulation of inflammatory cytokine gene expression in serum amyloid A-stimulated macrophages[J]. Cellular Signalling,2014,26(9):1783-1791.
APA Yan Q.,Sun L.,Zhu Z.,Wang L.,Li S.,&Ye R.D..(2014).Jmjd3-mediated epigenetic regulation of inflammatory cytokine gene expression in serum amyloid A-stimulated macrophages.Cellular Signalling,26(9),1783-1791.
MLA Yan Q.,et al."Jmjd3-mediated epigenetic regulation of inflammatory cytokine gene expression in serum amyloid A-stimulated macrophages".Cellular Signalling 26.9(2014):1783-1791.
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