title: Apurinic/apyrimidinic endonuclease1/redox factor-1 inhibits monocyte adhesion in endothelial cells.
abstract: OBJECTIVE
  Expression of adhesion molecules on endothelial cells and subsequent monocyte adhesion are initial events in the development of atherosclerosis. The purpose of this study was to investigate the role of apurinic/apyrmidinic endonuclease1/redox factor-1 (APE1/ref-1) in the interaction of monocytes with vascular endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were transfected with an adenovirus encoding human APE1/ref-1. The effect of APE1/ref-1 overexpression on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) protein expression, and intracellular superoxide production in tumor necrosis factor (TNF)-alpha-activated HUVECs was examined.
  
  
  RESULTS
  Adhesion of the monocytic cell line U937 to TNF-alpha-stimulated HUVECs in which APE1/ref-1 was overexpressed was suppressed. APE1/ref-1 overexpression also suppressed expression of VCAM-1 induced by TNF-alpha. APE1/ref-1-mediated suppression of VCAM-1 was blocked by pretreatment with the nitric oxide synthase (NOS) inhibitor l-nitroarginine methyl ester. Furthermore, APE1/ref-1 overexpression inhibited the TNF-alpha-induced increase in intracellular superoxide and p38 MAPK phosphorylation.
  
  
  CONCLUSIONS
  These data provide evidence that APE1/ref-1 in endothelial cells mitigates TNF-alpha-induced monocyte adhesion and expression of vascular cell adhesion molecules, and this anti-adhesive property of APE1/ref-1 is primarily mediated by a NOS-dependent mechanism. Furthermore, APE1/ref-1 may inhibit VCAM-1 expression by inhibiting superoxide production and p38 MAPK activation.
authors.affiliation: Department of Physiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-131 Korea.
authors.forename: Cuk Seong
authors.initials: CS
authors.lastname: Kim
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Son
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Seon Nyo
authors.initials: SN
authors.lastname: Kim
authors.forename: Dae Goon
authors.initials: DG
authors.lastname: Yoo
authors.forename: Hyo Shin
authors.initials: HS
authors.lastname: Kim
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Ryoo
authors.forename: Sang Do
authors.initials: SD
authors.lastname: Lee
authors.forename: Kaikobad
authors.initials: K
authors.lastname: Irani
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D018920:Coculture Techniques; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D019001:Nitric Oxide Synthase; D048051:p38 Mitogen-Activated Protein Kinases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D019331:NG-Nitroarginine Methyl Ester