title: N-octanoyl dopamine inhibits the expression of a subset of κB regulated genes: potential role of p65 Ser276 phosphorylation.
abstract: OBJECTIVE
  Catechol containing compounds have anti-inflammatory properties, yet for catecholamines these properties are modest. Since we have previously demonstrated that the synthetic dopamine derivative N-octanoyl dopamine (NOD) has superior anti-inflammatory properties compared to dopamine, we tested NOD in more detail and sought to elucidate the molecular entities and underlying mechanism by which NOD down-regulates inflammation.
  
  
  METHODS
  Genome wide gene expression profiling of human umbilical vein endothelial cells (HUVECs) was performed after stimulation with TNF-α or in the combination with NOD. Confirmation of these differences, NFκB activation and the molecular entities that were required for the anti-inflammatory properties were assessed in subsequent experiments.
  
  
  RESULTS
  Down regulation of inflammatory genes by NOD occurred predominantly for κB regulated genes, however not all κB regulated genes were affected. These findings were explained by inhibition of RelA phosphorylation at Ser276. Leukocyte adherence to TNF-α stimulated HUVECs was inhibited by NOD and was reflected by a diminished expression of adhesion molecules on HUVECs. NOD induced HO-1 expression, but this was not required for inhibition of NFκB. The anti-inflammatory effect of NOD seems to involve the redox active catechol structure, although the redox active para-dihydroxy benzene containing compounds also displayed anti-inflammatory effects, provided that they were sufficiently hydrophobic.
  
  
  CONCLUSIONS
  The present study highlighted important mechanisms and molecular entities by which dihydroxy benzene compounds exert their potential anti-inflammatory action. Since NOD does not have hemodynamic properties, NOD seems to be a promising candidate drug for the treatment of inflammatory diseases.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim, Ruprecht Karls University Heidelberg, Mannheim, Germany.
authors.forename: Maximilia C
authors.initials: MC
authors.lastname: Hottenrott
authors.forename: Johannes
authors.initials: J
authors.lastname: Wedel
authors.forename: Sophie
authors.initials: S
authors.lastname: Gaertner
authors.forename: Eleni
authors.initials: E
authors.lastname: Stamellou
authors.forename: Tineke
authors.initials: T
authors.lastname: Kraaij
authors.forename: Linda
authors.initials: L
authors.lastname: Mandel
authors.forename: Ralf
authors.initials: R
authors.lastname: Loesel
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.forename: Simone
authors.initials: S
authors.lastname: Hoeger
authors.forename: Lamia
authors.initials: L
authors.lastname: Ait-Hsiko
authors.forename: Angelika
authors.initials: A
authors.lastname: Schedel
authors.forename: Mathias
authors.initials: M
authors.lastname: Hafner
authors.forename: Benito
authors.initials: B
authors.lastname: Yard
authors.forename: Charalambos
authors.initials: C
authors.lastname: Tsagogiorgas
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000737:chemistry* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C554838:N-octanoyldopamine; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D012694:Serine; D004298:Dopamine
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