title: mRNA-binding protein ZFP36 is expressed in atherosclerotic lesions and reduces inflammation in aortic endothelial cells.
abstract: OBJECTIVE
  We studied the expression and function of an mRNA-binding protein, zinc finger protein-36 (ZFP36), in vascular endothelial cells in vivo and in vitro. We tested the hypotheses that ZFP36 regulates inflammation in vascular endothelial cells and that it functions through direct binding to target cytokine mRNAs. We also tested whether ZFP36 inhibits nuclear factor-κB-mediated transcriptional responses in vascular endothelial cells.
  
  
  RESULTS
  ZFP36 was minimally expressed in healthy aorta but was expressed in endothelial cells overlying atherosclerotic lesions in mice and humans. The protein was also expressed in macrophage foam cells of atherosclerosis. ZFP36 was expressed in human aortic endothelial cells in response to bacterial lipopolysaccharide, glucocorticoid, and forskolin, but not oxidized low-density lipoproteins or angiotensin II. Functional studies demonstrated that ZFP36 reduces the expression of inflammatory cytokines in target cells by 2 distinct mechanisms: ZFP36 inhibits nuclear factor-κB transcriptional activation and also binds to cytokine mRNAs, leading to reduced transcript stability.
  
  
  CONCLUSIONS
  ZFP36 is expressed in vascular endothelial cells and macrophage foam cells where it inhibits the expression of proinflammatory mRNA transcripts. The anti-inflammatory effects of ZFP36 in endothelial cells occur via both transcriptional and posttranscriptional mechanisms. Our data suggest that enhancing vascular ZFP36 expression might reduce vascular inflammation.
authors.affiliation: Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Zhang
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.forename: Giji
authors.initials: G
authors.lastname: Joseph
authors.forename: Valentina
authors.initials: V
authors.lastname: Caracciolo
authors.forename: Donna M
authors.initials: DM
authors.lastname: Gonzales
authors.forename: Neil
authors.initials: N
authors.lastname: Sidell
authors.forename: Emre
authors.initials: E
authors.lastname: Seli
authors.forename: Perry J
authors.initials: PJ
authors.lastname: Blackshear
authors.forename: Caleb B
authors.initials: CB
authors.lastname: Kallen
mesh_terms: D000818:Animals; D001011:Aorta; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D051816:Tristetraprolin / Q000235:genetics*; D014657:Vasculitis / Q000235:genetics / Q000517:prevention & control
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D012333:RNA, Messenger; D051816:Tristetraprolin
keywords: AU-rich element; atherosclerosis; cytokines; endothelial cell; inflammation; zinc finger protein-36
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