Tumor necrosis factor-α up-regulates glucuronosyltransferase gene expression in human brain endothelial cells and promotes T-cell adhesion

Somsankar Dasgupta, Makoto Yanagisawa, Kannan Rrishnamurthy, Sean S. Liour, Robert K Yu

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Stimulation of human brain microvascular endothelial cells (SV-HCECs) with tumor necrosis factor-α (TNF-α) up-regulates sulfoglucuronosyl paragloboside (SGPG) synthesis in a dose- and time-dependent manner. After TNF-α exposure at a concentration of 50 ng/ml for 24 hr, we observed a seven- to tenfold elevation of SGPG concentration. Interleukin-1β (IL-1β) at a concentration of 10 ng/ml and the combined doses of TNF-α and IL-1β were less effective than TNF-α alone. TNF-α also stimulated T-cell (Jurkat) adhesion with SV-HCECs via SGPG-L-selectin recognition: this was determined by double-label immunofluorescent staining with SGPG and L-selectin antibodies. The number of T cells bound to SV-HCECs after different cytokine stimulations was proportional to the SGPG concentration, and the cell attachment was inhibited by anti-SGPG and anti-L-selectin antibodies, respectively. Our data unequivocally establish that inflammatory cytokines, particularly TNF-α, stimulate the glucuronosyltransferse, GlcAT-P, and GlcAT-S, gene expression in brain endothelial cells and promote T-cell adhesion via SGPG-L-selectin recognition, a preliminary step for onset of neuroinflammation.

Original languageEnglish (US)
Pages (from-to)1086-1094
Number of pages9
JournalJournal of Neuroscience Research
Volume85
Issue number5
DOIs
StatePublished - Apr 1 2007

Keywords

  • Cell adhesion
  • Endothelial cells
  • Glycosphingolipids
  • Inflammatory cytokines
  • L-selectin
  • Neurodegeneration

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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