Colonic epithelial cells induce endothelial cell expression of ICAM-1 and VCAM-1 by a NF-kappaB-dependent mechanism.
Epithelial cells are positioned in close proximity to endothelial cells. A non-contact coculture system was used to investigate whether colonic epithelial cells activated with various cytokines are able to provide signals that can modulate ICAM-1 and VCAM-1 expression on endothelial cells. Coculture of human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) with TNF-alpha/IFN-gamma-stimulated human colon epithelial cell lines led to a significant up-regulation of endothelial ICAM-1 and VCAM-1 expression. Increased ICAM-1 and VCAM-1 expression by endothelial cells was accompanied by an increase in endothelial cell NF-kappaB p65 and NF-kappaB-DNA-binding activity. Inhibition of endothelial NF-kappaB activation using the proteosome inhibitors MG-132 and BAY 11-7082 resulted in a significant decrease of ICAM-1 expression, indicating an important role for NF-kappaB in this response. This cross-talk may represent a biological mechanism for the gut epithelium to control the colonic inflammatory response and the subsequent immune cell recruitment during inflammation.
Maaser
C
C
Department of Medicine B, and Department of Biochemistry and Pathobiochemistry, University of Münster, Münster, Germany.
Schoeppner
S
S
Kucharzik
T
T
Kraft
M
M
Schoenherr
E
E
Domschke
W
W
Luegering
N
N
D018938:Caco-2 Cells; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003106:Colon / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D008833:Microcirculation / Q000166:cytology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1