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Am J Physiol Gastrointest Liver Physiol 278: G734-G743, 2000;
0193-1857/00 $5.00
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Vol. 278, Issue 5, G734-G743, May 2000

Cytokine and endothelial cell adhesion molecule expression in interleukin-10-deficient mice

Shigeyuki Kawachi1, Stephen Jennings2, Julian Panes3, Adam Cockrell1, F. Stephen Laroux1, Laura Gray1, Michael Perry4, Henry van der Heyde2, Edward Balish5, D. Neil Granger1, Robert A. Specian1, and Matthew B. Grisham1

Departments of 1 Molecular and Cellular Physiology and 2 Microbiology and Immunology, Louisiana State University Medical Center, Shreveport, Louisiana 71130; 3 Department of Gastroenterology, University of Barcelona, Barcelona, Spain; 4 School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia; and 5 Department of Surgery, University of Wisconsin, Madison, Wisconsin 53706

The objectives of this study were to quantify cytokine mRNA levels and endothelial cell adhesion molecule message and protein expression in healthy wild-type and interleukin-10-deficient (IL-10-/-) mice that develop spontaneous and chronic colitis. We found that colonic message levels of IL-1, IL-6, tumor necrosis factor-alpha , interferon-gamma , lymphotoxin-beta , and transforming growth factor-beta were elevated in colitic mice 10- to 35-fold compared with their healthy wild-type controls. In addition, colonic message levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) were found to be increased 10-, 5-, and 23-fold, respectively, in colitic IL-10-/- mice compared with their wild-type 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. These data are consistent with the hypothesis that deletion of IL-10 results in the sustained production of proinflammatory cytokines, leading to the upregulation of adhesion molecules and infiltration of mononuclear and polymorphonuclear leukocytes into the cecal and colonic interstitium.

leukocytes; inflammation; immunology


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