title: Sulforaphane inhibits endothelial lipase expression through NF-κB in endothelial cells.
abstract: OBJECTIVE
  Endothelial lipase (EL) is a new member of triacylglycerol lipase family that has been shown to decrease high-density lipoprotein (HDL) cholesterol levels leading to increased risk of atherosclerosis. Its expression is increased during inflammation and by inflammatory cytokines. Sulforaphane (SFN) is a naturally occurring isothiocyanate present in cruciferous vegetables that has antioxidant and anti-inflammatory effects. Nuclear factor (NF)-κB is one of the molecular targets for SFN-mediated protective effects. Our aim was therefore to assess whether SFN could impact on EL expression via modulation of NF-κB pathway.
  
  
  RESULTS
  Quantitative PCR and Western blot results demonstrated that SFN inhibited tumor necrosis factor (TNF)-α-mediated induction of EL in human umbilical vein endothelial cells (HUVEC). Lentiviral transduction of HUVEC with mutated form of IκB-α (IκBM) as well as silencing of NF-κB subunit p65 using RNA interference revealed that TNF-α-mediated induction of EL is mediated through NF-κB pathway. In addition, a total of five NF-κB binding sites were found in LIPG gene, which encodes EL. SFN inhibited binding of NF-κB to these sites analyzed by chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). SFN also inhibited TNF-α mediated phosphorylation of IκB kinase (IKK) 1/2 and IκB-α.
  
  
  CONCLUSIONS
  Collectively, these results indicate that SFN inhibits EL expression via inhibition of NF-κB which may have a beneficial effect on HDL cholesterol levels.
authors.affiliation: The Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Neulaniementie 2, FIN-70211 Kuopio, Finland.
authors.forename: Annukka M
authors.initials: AM
authors.lastname: Kivelä
authors.forename: Petri I
authors.initials: PI
authors.lastname: Mäkinen
authors.forename: Henna-Kaisa
authors.initials: HK
authors.lastname: Jyrkkänen
authors.forename: Eero
authors.initials: E
authors.lastname: Mella-Aho
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Emilia
authors.initials: E
authors.lastname: Kansanen
authors.forename: Hanna
authors.initials: H
authors.lastname: Leinonen
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Levonen
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D050197:Atherosclerosis / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D017879:Isothiocyanates / Q000737:chemistry; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D014675:Vegetables
chemical_list: D000975:Antioxidants; D017879:Isothiocyanates; D016328:NF-kappa B; D013454:Sulfoxides; D013861:Thiocyanates; D051550:I-kappa B Kinase; C410382:LIPG protein, human; D008049:Lipase; C016766:sulforaphane