title: Melatonin reduces TNF-a induced expression of MAdCAM-1 via inhibition of NF-kappaB.
abstract: BACKGROUND
  Endothelial MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the oxidant-dependent induction and progress of inflammatory bowel disease (IBD). Melatonin, a relatively safe, potent antioxidant, has shown efficacy in several chronic injury models may limit MAdCAM-1 expression and therefore have a therapeutic use in IBD.
  
  
  METHODS
  We examined how different doses of melatonin reduced endothelial MAdCAM-1 induced by TNF-a in an in vitro model of lymphatic endothelium. Endothelial monolayers were pretreated with melatonin prior to, and during an exposure, to TNF-a (1 ng/ml, 24 h), and MAdCAM-1 expression measured by immunoblotting.
  
  
  RESULTS
  MAdCAM-1 was induced by TNF-a. Melatonin at concentrations over 100 microm (10(-4) M) significantly attenuated MAdCAM-1 expression and was maximal at 1 mM.
  
  
  CONCLUSIONS
  Our data indicate that melatonin may exert therapeutic activity in IBD through its ability to inhibit NF-kappaB dependent induction of MAdCAM-1.
authors: LSU Health Sciences Center-Shreveport Molecular and Cellular Physiology, 1501 Kings Highway, Shreveport, Louisiana 71130-3932, USA. msasak@lsuhsc.edu
authors: Makoto
authors: M
authors: Sasaki
authors: Paul
authors: P
authors: Jordan
authors: Takashi
authors: T
authors: Joh
authors: Makotoh
authors: M
authors: Itoh
authors: Michael
authors: M
authors: Jenkins
authors: Kevin
authors: K
authors: Pavlick
authors: Alireza
authors: A
authors: Minagar
authors: Steven J
authors: SJ
authors: Alexander
mesh_terms: D015815:Cell Adhesion Molecules; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004729:Endothelium, Lymphatic / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins; D008550:Melatonin / Q000494:pharmacology*; D009088:Mucoproteins / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D016328:NF-kappa B; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D008550:Melatonin