Cytokines modulate endothelial cell intracellular signal transduction required for VCAM-1-dependent lymphocyte transendothelial migration

Kim Sue R S Tudor, Krista L. Hess, Joan M. Cook-Mills*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Vascular cell adhesion molecule-1 (VCAM-1) activates endothelial cell NADPH oxidase which catalyzes production of reactive oxygen species (ROS). This activity is required for VCAM-1-dependent lymphocyte migration. The focus of our study was to determine whether these VCAM-1-dependent functions are modulated by cytokines. TGF-β1 or IFN-γ pretreatment of mouse endothelial cell lines inhibited VCAM-1-dependent B and T cell transendothelial migration without affecting initial lymphocyte adhesion. Neutralizing anti-TGF-β1 blocked the effects of TGF-β1 pretreatment of endothelial cells, whereas addition of anti-TGF-β1 after TGF-β1 pretreatment of the endothelial cells did not block TGF-β1-mediated inhibition. Neutralizing anti-IFN-γ also blocked the inhibitory effects of IFN-γ. TGF-β1 and IFN-γ blocked migration by inhibiting the VCAM-1-stimulated production of low levels of ROS (0.1-0.9 μM H2O2). These results demonstrate that both TGF-β1 and IFN-γ directly affect the endothelial cells' ability to promote lymphocyte migration. IL-4 had differing effects on T and B cells during transmigration. IL-4 augmented T cell migration across the endothelial cell lines but did not affect T cell adhesion. Conversely, IL-4 increased B cell adhesion to the endothelial cell lines without affecting migration. In summary, cytokines can directly modulate microvascular endothelial cell intracellular signaling, demonstrating a new level of cytokine regulation of lymphocyte diapedesis.

Original languageEnglish (US)
Pages (from-to)196-211
Number of pages16
JournalCytokine
Volume15
Issue number4
DOIs
StatePublished - Aug 21 2001

Keywords

  • B lymphocytes
  • Cytokines
  • Endothelial cells
  • Migration
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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