title: Role of 3beta-hydroxysteroid-delta 24 reductase in mediating antiinflammatory effects of high-density lipoproteins in endothelial cells.
abstract: OBJECTIVE
  The purpose of this study was to investigate the ability of high-density lipoproteins (HDLs) to upregulate genes with the potential to protect against inflammation in endothelial cells.
  
  
  RESULTS
  Human coronary artery endothelial cells (HCAECs) were exposed to reconstituted HDLs (rHDLs) for 16 hours before being activated with tumor necrosis factor-alpha (TNF-alpha) for 5 hours. rHDLs decreased vascular cell adhesion molecule-1 (VCAM-1) promoter activity by 75% (P<0.05), via the nuclear factor-kappa B (NF-kappaB) binding site. rHDLs suppressed the canonical NF-kappaB pathway and decreased many NF-kappaB target genes. Suppression of NF-kappaB and VCAM-1 expression by rHDLs or native HDLs was dependent on an increase in 3beta-hydroxysteroid-Delta 24 reductase (DHCR24) levels (P<0.05). The effect of HDLs on DHCR24 is dependent on SR-BI but not ABCAI or ABCGI. Silencing DHCR24 expression increased NF-kappaB (1.2-fold, P<0.05), VCAM-1 (30-fold, P<0.05), and NF-kappaB p50 (4-fold, P<0.05) and p65 subunits (150-fold, P<0.05). TNF-alpha activation of siDHCR24-treated cells increased expression of VCAM-1 (550-fold, P<0.001) and NF-kappaB (9-fold, P<0.001) that could no longer be suppressed by rHDLs.
  
  
  CONCLUSIONS
  Results suggest that antiinflammatory effects of rHDLs are mediated partly through an upregulation of DHCR24. These findings raise the possibility of considering DHCR24 as a target for therapeutic modulation.
authors.affiliation: Heart Research Institute, 114 Pyrmont Bridge Road, Camperdown, NSW, 2050, Australia.
authors.forename: K C Y
authors.initials: KC
authors.lastname: McGrath
authors.forename: X H
authors.initials: XH
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Puranik
authors.forename: E C
authors.initials: EC
authors.lastname: Liong
authors.forename: J T M
authors.initials: JT
authors.lastname: Tan
authors.forename: V M
authors.initials: VM
authors.lastname: Dy
authors.forename: B A
authors.initials: BA
authors.lastname: DiBartolo
authors.forename: P J
authors.initials: PJ
authors.lastname: Barter
authors.forename: K A
authors.initials: KA
authors.lastname: Rye
authors.forename: A K
authors.initials: AK
authors.lastname: Heather