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

S Kawachi, S Jennings, J Panes… - American Journal …, 2000 - journals.physiology.org
S Kawachi, S Jennings, J Panes, A Cockrell, FS Laroux, L Gray, M Perry, H van der Heyde…
American Journal of Physiology-Gastrointestinal and Liver …, 2000journals.physiology.org
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-α, interferon-γ, lymphotoxin-β, and
transforming growth factor-β were elevated in colitic mice 10-to 35-fold compared with their
healthy wild-type controls. In addition, colonic message levels of intercellular adhesion …
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-α, interferon-γ, lymphotoxin-β, and transforming growth factor-β 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.
American Physiological Society