Adhesion Molecule Expression in Inflammatory Bowel Disease
Research field:Gastrointestinal physiology
Authors:Grisham MB, Kawachi S, Laroux S, Gray L, Fuseler J
Address of presenting
author:		Department of Molecular and Cellular Physiology
Louisiana State University Health Sciences Center
1501 Kings Highway
Shreveport, Louisiana 71130
E-mail:mgrish@lsumc.edu
Phone:318-675-6021
Fax:318-675-4156
Text of abstract Introduction
Inflammatory bowel disease (IBD) is a recurrent inflammation of the small and/or large bowel of unknown etiology. Recent experimental studies suggest that IBD may result from a dysregulated immune response to components of the normal gut flora resulting in the sustained overproduction of Th1 and macrophage-derived cytokines. Although these pro-inflammatory cytokines are thought to initiate and/or perpetuate chronic gut inflammation by virtue of their ability to upregulate the surface expression of different endothelial cell adhesion molecules (ECAMs) no systematic nor quantitative information is available regarding the relatioship between cytokine and ECAM expression in a model of IBD in vivo.

Methods
Message levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and mucosal cell addressin molecule-1 (MAdCAM-1)message levels as well as message levels for the different Th1 and macrophage-derived cytokines were quantified in wild type (129 SvEv) or IL-10 deficient mice (IL-10 -/-)at three months of age using the ribonuclease protection assay (RPA). Protein surface expression of the different ECAMs was quantified in the living animal using the dual radiolabel monoclonal antidbody techniqe.

Results
We found that colonic message levels of IL-1, IL-6, TNF-a, IF-g, LT-b and TGF-b were elevated in colitic mice 10-35 fold compared to their healthy wt controls. In addition, colonic message levels of ICAM-1, VCAM-1, and MAdCAM-1 were found to be increased 10, 5 and 23-fold, respectively in colitic IL-10-/- mice compared to their wt controls. Immunoradiolabeling as well as immunohistochemistry revealed large and significant increases in vascular surface expression of colonic ICAM-1, VCAM-1 and MAdCAM-1 in the mucosa as well as the submucosa of the colons of colitic mice.

Conclusions
These data are consistent with the hypothesis that deletion of IL-10 results in the dysregulation of immune response of the gut leading to the up-regulation of a number of different pro-inflammatory cytokines. This uncontrolled Th1 type response ultimately leads to the upregulation of adhesion molecules and infiltration of potentially injurious and immune modifying mononuclear and polymorphonuclear leukocytes into the cecal and colonic interstitium.

References

Keywords:leukocytes, colitis, inflammation, immune system

Created 2000-04-22