Faculty Collaboration Database

Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells. Am J Physiol Cell Physiol 2005 Feb;288(2):C272-81

Date

10/16/2004

Pubmed ID

15483224

DOI

10.1152/ajpcell.00406.2003

Scopus ID

2-s2.0-12144271043 (requires institutional sign-in at Scopus site)   54 Citations

Abstract

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a homing receptor preferentially expressed on gut-associated endothelial cells that plays a central role in leukocyte traffic into the mucosal immune compartment. Although the molecular mechanisms underlying endothelial ICAM-1 or E-selectin expression have been intensively investigated, the mechanisms that regulate human MAdCAM-1 expression have not been defined. We report MAdCAM-1 gene and protein expression in primary cultures of human intestinal microvascular endothelial cells (HIMEC) that was not demonstrated in human umbilical vein endothelial cells. Similar to ICAM-1 and E-selectin expression, MAdCAM-1 gene expression in HIMEC was inducible with TNF-alpha, IL-1beta, or LPS activation. However, in striking contrast to ICAM-1 and E-selectin expression, MAdCAM-1 mRNA and protein expression in HIMEC was heavily dependent on culture duration and/or cellular density, suggesting a prominent role for cell-cell interaction among these endothelial cells in the expression of the mucosal addressin. MAdCAM-1 expression was inhibited by both SN-50 (NF-kappaB inhibitor) and LY-294002 [phosphatidylinositol 3-kinase (PI3-K) inhibitor], whereas ICAM-1 and E-selectin expression was inhibited by SN-50 but not by LY-294002. The Akt phosphorylation by TNF-alpha or LPS was greater at higher cell density, demonstrating a pattern similar to that of MAdCAM-1 expression. NF-kappaB activation was not affected by cellular density in HIMEC. MAdCAM-1 expression in human gut endothelial cells is regulated by distinct signaling mechanisms involving both NF-kappaB and PI3-K/Akt. These data also suggest that PI3-K/Akt is involved in the gut-specific differentiation of HIMEC, which results in expression of the mucosal addressin MAdCAM-1.

Author List

Ogawa H, Binion DG, Heidemann J, Theriot M, Fisher PJ, Johnson NA, Otterson MF, Rafiee P

Author

Mary F. Otterson MS, MD Emeritus Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antigens, Surface
Blotting, Western
Cell Adhesion Molecules
Cells, Cultured
E-Selectin
Electrophoretic Mobility Shift Assay
Endothelial Cells
Fluorescent Antibody Technique
Gene Expression
Humans
Immunoglobulins
Intercellular Adhesion Molecule-1
Intestinal Mucosa
Membrane Proteins
Mucoproteins
NF-kappa B
Phosphatidylinositol 3-Kinases
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction