Regulation and distribution of MAdCAM-1 in endothelial cells in vitro

Am J Physiol Cell Physiol. 2001 Oct;281(4):C1096-105. doi: 10.1152/ajpcell.2001.281.4.C1096.

Abstract

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a 60-kDa endothelial cell adhesion glycoprotein that regulates lymphocyte trafficking to Peyer's patches and lymph nodes. Although it is widely agreed that MAdCAM-1 induction is involved in chronic gut inflammation, few studies have investigated regulation of MAdCAM-1 expression. We used two endothelial lines [bEND.3 (brain) and SVEC (high endothelium)] to study the signal paths that regulate MAdCAM-1 expression in response to tumor necrosis factor (TNF)-alpha using RT-PCR, blotting, adhesion, and immunofluorescence. TNF-alpha induced both MAdCAM-1 mRNA and protein in a dose- and time-dependent manner. This induction was tyrosine kinase (TK), p42/44, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-kappa B/poly-ADP ribose polymerase (PARP) dependent. Because MAdCAM-1 is regulated via MAPKs, we examined mitogen/extracellular signal-regulated kinase (MEK)-1/2 activation in SVEC. We found that MEK-1/2 is activated by TNF-alpha within minutes and is dependent on TK and p42/44 MAPKs. Similarly, TNF-alpha activated NF-kappa B through TK, p42/44, p38 MAPKs, and PARP pathways in SVEC cells. MAdCAM-1 was also shown to be frequently distributed to endothelial junctions both in vitro and in vivo. Cytokines like TNF-alpha stimulate MAdCAM-1 in high endothelium via TK, p38, p42/22 MAPKs, and NF-kappa B/PARP. MAdCAM-1 expression requires NF-kappa B translocation through both direct p42/44 and indirect p38 MAPK pathways in high endothelial cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Benzophenanthridines
  • Benzopyrans / pharmacology
  • Carbazoles*
  • Cell Adhesion Molecules
  • Cell Line, Transformed
  • Cysteine Proteinase Inhibitors / pharmacology
  • Endothelium / chemistry
  • Endothelium / cytology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Genistein / pharmacology
  • Imidazoles / pharmacology
  • Immunoglobulins / analysis*
  • Immunoglobulins / genetics*
  • In Vitro Techniques
  • Indoles*
  • Inflammatory Bowel Diseases / physiopathology
  • Intestinal Mucosa / chemistry*
  • Intestinal Mucosa / cytology*
  • Isoquinolines / pharmacology
  • Leupeptins / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Mice
  • Mucoproteins / analysis*
  • Mucoproteins / genetics*
  • NF-kappa B / antagonists & inhibitors
  • Phenanthridines / pharmacology
  • Pyridines / pharmacology
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Alkaloids
  • Benzophenanthridines
  • Benzopyrans
  • Carbazoles
  • Cell Adhesion Molecules
  • Cysteine Proteinase Inhibitors
  • Enzyme Inhibitors
  • Flavonoids
  • GPI 6150
  • Imidazoles
  • Immunoglobulins
  • Indoles
  • Isoquinolines
  • Leupeptins
  • Madcam1 protein, mouse
  • Mucoproteins
  • NF-kappa B
  • Phenanthridines
  • Pyridines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • KT 5823
  • Genistein
  • chelerythrine
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one