title: Dextromethorphan attenuates LPS-induced adhesion molecule expression in human endothelial cells.
abstract: OBJECTIVE
  This study examines the effect of Dextromethorphan (d-3-methoxy-17-methylmorphinan; DXM), a commonly used cough-suppressing drug, on the expression of VCAM-1 and ICAM-1 in human umbilical vein endothelial cells (HUVECs) stimulated with lipopolysaccharide (LPS).
  
  
  METHODS
  The effect of DXM on expression of cell adhesion molecules induced by LPS was evaluated by monocyte bindings in vitro and ex vivo and transmigration assays. The signaling pathways involved in the inflammation inhibitory effect of DXM were analyzed by Western blot and immunofluorescent stain.
  
  
  RESULTS
  Pretreatment of HUVECs with DXM inhibited LPS-induced adhesion of THP-1 cells in vitro and ex vivo, and reduced transendothelial migration of these cells. Furthermore, treatment of HUVECs with DXM can significantly decrease LPS-induced expression of ICAM-1 and VCAM-1. DXM abrogated LPS-induced phosphorylation of ERK and Akt. The translocation of early growth response gene-1 (Egr-1), a downstream transcription factor involved in the mitogen-activated kinase (MEK)-ERK signaling pathway, was suppressed by DXM treatment. Furthermore, DXM inhibited LPS-induced IκBα degradation and nuclear translocation of p65.
  
  
  CONCLUSIONS
  Dextromethorphan inhibits the adhesive capacity of HUVECs by reducing the LPS-induced ICAM-1 and VCAM-1 expression via the suppression of the ERK, Akt, and NF-κB signaling pathways. Thus, DXM is a potential anti-inflammatory therapeutic that may modulate atherogenesis.
authors.affiliation: Department of Biochemistry, College of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Shinn-Jong
authors.initials: SJ
authors.lastname: Jiang
authors.forename: Sheng-Yao
authors.initials: SY
authors.lastname: Hsu
authors.forename: Chuan-Rou
authors.initials: CR
authors.lastname: Deng
authors.forename: Huey-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Liu
authors.forename: Guey-Yueh
authors.initials: GY
authors.lastname: Shi
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Wu
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003915:Dextromethorphan / Q000494:pharmacology*; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D018691:Excitatory Amino Acid Antagonists; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003915:Dextromethorphan; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt