Modulation of pyrogen-induced upregulation of endothelial cell adhesion molecules (CAMs) by interleukin-4: transcriptional mechanisms and CAM-shedding

Circ Shock. 1994 May;43(1):18-25.

Abstract

The pyrogens interleukin 1 (IL-1), tumor necrosis factor (TNF), and bacterial lipopolysaccharides (LPS) are known to increase endothelial cell (EC) adhesiveness for leukocytes by stimulating surface expression of various adhesion molecules. IL-4, a product of activated T-cells, was shown to affect pyrogen-mediated regulation of EC adhesion molecule surface expression. In the present study, we investigated the effect of IL-4 on pyrogen-induced upregulation of the cell adhesion molecules (CAMs) ICAM-1 (intercellular cell adhesion molecule-1), ELAM-1 (endothelial leucocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1) in cultured human umbilical vein EC (HUVEC). Surface expression of adhesion molecules was quantified by flow cytometry, HUVEC mRNA content was estimated by Northern blot analysis, and ICAM-1 antigen in conditioned media was measured by ELISA. Incubation of HUVEC with IL-1 (100 U/ml), TNF (500 U/ml), and LPS (10 micrograms/ml) caused significant increase in ICAM-1, ELAM-1, and VCAM-1 surface expression; IL-1 caused about an eightfold increase in ICAM-1 expression, about a 13-fold increase in ELAM-1 surface expression, and about a fourfold increase in VCAM-1 expression. Coincubation of pyrogens with IL-4 (500 U/ml) differentially influenced their proadhesive effects on the HUVEC surface. In the presence of IL-4, IL-1-induced ICAM-1 upregulation was reduced, ELAM-1 upregulation was not significantly influenced by IL-4, and induction of VCAM-1 was enhanced by IL-4.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • E-Selectin
  • Endothelium, Vascular / metabolism*
  • Escherichia coli
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1 / pharmacology
  • Interleukin-4 / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Molecular Sequence Data
  • Pyrogens / pharmacology*
  • RNA, Messenger / metabolism
  • Transcription, Genetic*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins
  • Vascular Cell Adhesion Molecule-1

Substances

  • Cell Adhesion Molecules
  • E-Selectin
  • Interleukin-1
  • Lipopolysaccharides
  • Pyrogens
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interleukin-4