Cytokine and endothelial cell adhesion molecule expression in interleukin-10-deficient mice.
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.
Kawachi
S
S
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA.
Jennings
S
S
Panes
J
J
Cockrell
A
A
Laroux
F S
FS
Gray
L
L
Perry
M
M
van der Heyde
H
H
Balish
E
E
Granger
D N
DN
Specian
R A
RA
Grisham
M B
MB
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000276:immunology*; D007136:Immunoglobulins / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D009088:Mucoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007136:Immunoglobulins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10