Melatonin reduces TNF-a induced expression of MAdCAM-1 via inhibition of NF-kappaB.
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.
Sasaki
Makoto
M
LSU Health Sciences Center-Shreveport Molecular and Cellular Physiology, 1501 Kings Highway, Shreveport, Louisiana 71130-3932, USA. msasak@lsuhsc.edu
Jordan
Paul
P
Joh
Takashi
T
Itoh
Makotoh
M
Jenkins
Michael
M
Pavlick
Kevin
K
Minagar
Alireza
A
Alexander
Steven J
SJ
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*
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