Sulfoglucuronosyl paragloboside is a ligand for T cell adhesion: regulation of sulfoglucuronosyl paragloboside expression via nuclear factor kappaB signaling

J Neurosci Res. 2009 Dec;87(16):3591-9. doi: 10.1002/jnr.22153.


Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta stimulate glucuronosyltransferase genes (S and P) in endothelial cells (ECs) and up-regulate sulfoglucuronosyl paragloboside (SGPG) expression, which serves as a ligand for T cell adhesion. However, the mechanism of cytokine-mediated gene up-regulation has not been elucidated. To evaluate the precise mechanism of SGPG up-regulation, we have specifically inhibited the SGPG synthesis in the cerebromicrovascular EC line (SV-HCECs), a transformed brain ECs of human origin. SV-HCECs were transfected with small interfering RNA designed to mimic the human natural killer epitope-1 sulfotransferase (HNK-1ST), the ultimate enzyme that transfers the sulfate group to glucuronic acid for SGPG synthesis. An inhibition of SGPG expression along with a reduction of human CD4(+) cell adhesion was observed in siRNA HNK-1ST (siHNK-1)-transfected cells after TNFalpha stimulation. A thorough screening of the signaling system confirmed that TNFalpha/IL-1beta stimulation up-regulated nuclear factor kappaB (NFkappaB) signaling in SV-HCECs. siHNK-1 transfection interfered with the SGPG up-regulation after TNFalpha/IL-1beta stimulation in transfected cells and reduced the T cell adhesion. Hence, our study indicates that T cell-SGPG adhesion in SV-HCECs may proceed through NFkappaB activation. In addition, siHNK-1 transfection reduced the NFkappaB activity compared with cells that were transfected with scrambled siRNA, before and after TNFalpha/IL-1beta stimulation. This is the first report indicating that NFkappaB signaling is involved in SGPG gene expression in brain ECs by an unknown mechanism. Its down-regulation by inhibiting HNK-1ST expression may have a potential use in preventing the T cell invasion and consequently nerve damage during inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism*
  • CD4 Antigens
  • Cell Adhesion / drug effects
  • Cell Line
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Globosides / genetics
  • Globosides / metabolism*
  • Humans
  • Immunohistochemistry
  • Interleukin-1beta / metabolism
  • NF-kappa B / metabolism*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Sulfotransferases / genetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics


  • CD4 Antigens
  • Globosides
  • Interleukin-1beta
  • NF-kappa B
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • sulfate-3-glucuronyl paragloboside
  • CHST10 protein, human
  • Sulfotransferases