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TNF-alpha induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide

T Oshima1, P Jordan, M B Grisham

  • 1Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, Louisiana, USA. toshim@lsumc.edu

BMC Gastroenterology
|August 2, 2001
PubMed

Insights

Exogenous nitric oxide (NO) donors inhibit TNF-alpha-induced MAdCAM-1 expression, potentially benefiting inflammatory bowel disease (IBD) treatment. Endogenous NO production appears less effective in regulating this adhesion molecule.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) is crucial for lymphocyte homing to the gut, particularly in inflammatory bowel disease (IBD).
  • Tumor necrosis factor-alpha (TNF-alpha) mobilizes MAdCAM-1 expression, influencing gut-specific lymphocyte trafficking.
  • Reactive oxygen and nitrogen species are implicated in regulating adhesion molecule expression following cytokine stimulation.

Purpose of the Study:

  • To investigate the modulatory effects of exogenous and endogenous nitric oxide (NO) on TNF-alpha-induced MAdCAM-1 expression.
  • To assess the impact of NO on lymphocyte adhesion to endothelial cells.

Main Methods:

  • Mouse lymphatic endothelial cells were pre-treated with NO donors (long or short-acting) before TNF-alpha stimulation.
  • MAdCAM-1 expression and lymphocyte-endothelial cell adhesion were measured.
  • Inhibition of endogenous NO production was achieved using NOS inhibitors (L-NAME, 1400w).

Main Results:

  • Both long-acting (DETA-NO) and rapid-releasing (SperNO) NO donors significantly inhibited TNF-alpha-stimulated MAdCAM-1 expression in a dose-dependent manner.
  • Exogenous NO donors reduced alpha4beta7-dependent lymphocyte adhesion to endothelial cells.
  • Inhibition of endogenous NO production did not alter or potentiate TNF-alpha-regulated MAdCAM-1 expression.

Conclusions:

  • Exogenous NO donors demonstrate potential therapeutic value for IBD by suppressing MAdCAM-1 expression.
  • Endogenous nitric oxide synthases appear less critical for controlling cytokine-induced adhesion molecule expression in this context.
Abstract

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