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

Somsankar Dasgupta, Maria J Silva, Guanghu Wang, Robert K Yu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β stimulate glucuronosyl-transferase 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 sulfo-transferase (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 TNFa stimulation. A thorough screening of the signaling system confirmed that TNFαa/IL-1β stimulation up-regulated nuclear factor κB (NFκB) signaling in SV-HCECs. siHNK-1 transfection interfered with the SGPG up-regulation after TNFα/IL-1β 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 NFκB activation. In addition, siHNK-1 transfection reduced the NFκB activity compared with cells that were transfected with scrambled siRNA, before and after TNFα/IL-1β stimulation. This is the first report indicating that NFκB 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.

Original languageEnglish (US)
Pages (from-to)3591-3599
Number of pages9
JournalJournal of Neuroscience Research
Volume87
Issue number16
DOIs
StatePublished - Dec 1 2009

Fingerprint

Cell Adhesion
Ligands
T-Lymphocytes
Small Interfering RNA
Transferases
Interleukin-1
Up-Regulation
Endothelial Cells
Epitopes
Tumor Necrosis Factor-alpha
Transfection
Cytokines
Glucuronic Acid
sulfate-3-glucuronyl paragloboside
Brain
Genes
Sulfates
Down-Regulation
Inflammation
Gene Expression

Keywords

  • Blood-brain/nerve barrier
  • Endothelial cell
  • Glycosphingolipid
  • Human natural killer antigen
  • NFκB signaling

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

@article{0fdb507812994cd6b080ad9547896454,
title = "Sulfoglucuronosyl paragloboside is a ligand for T cell adhesion: Regulation of sulfoglucuronosyl paragloboside expression via nuclear factor κB signaling",
abstract = "Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β stimulate glucuronosyl-transferase 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 sulfo-transferase (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 TNFa stimulation. A thorough screening of the signaling system confirmed that TNFαa/IL-1β stimulation up-regulated nuclear factor κB (NFκB) signaling in SV-HCECs. siHNK-1 transfection interfered with the SGPG up-regulation after TNFα/IL-1β 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 NFκB activation. In addition, siHNK-1 transfection reduced the NFκB activity compared with cells that were transfected with scrambled siRNA, before and after TNFα/IL-1β stimulation. This is the first report indicating that NFκB 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.",
keywords = "Blood-brain/nerve barrier, Endothelial cell, Glycosphingolipid, Human natural killer antigen, NFκB signaling",
author = "Somsankar Dasgupta and Silva, {Maria J} and Guanghu Wang and Yu, {Robert K}",
year = "2009",
month = "12",
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doi = "10.1002/jnr.22153",
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volume = "87",
pages = "3591--3599",
journal = "Journal of Neuroscience Research",
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T1 - Sulfoglucuronosyl paragloboside is a ligand for T cell adhesion

T2 - Regulation of sulfoglucuronosyl paragloboside expression via nuclear factor κB signaling

AU - Dasgupta, Somsankar

AU - Silva, Maria J

AU - Wang, Guanghu

AU - Yu, Robert K

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β stimulate glucuronosyl-transferase 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 sulfo-transferase (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 TNFa stimulation. A thorough screening of the signaling system confirmed that TNFαa/IL-1β stimulation up-regulated nuclear factor κB (NFκB) signaling in SV-HCECs. siHNK-1 transfection interfered with the SGPG up-regulation after TNFα/IL-1β 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 NFκB activation. In addition, siHNK-1 transfection reduced the NFκB activity compared with cells that were transfected with scrambled siRNA, before and after TNFα/IL-1β stimulation. This is the first report indicating that NFκB 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.

AB - Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β stimulate glucuronosyl-transferase 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 sulfo-transferase (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 TNFa stimulation. A thorough screening of the signaling system confirmed that TNFαa/IL-1β stimulation up-regulated nuclear factor κB (NFκB) signaling in SV-HCECs. siHNK-1 transfection interfered with the SGPG up-regulation after TNFα/IL-1β 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 NFκB activation. In addition, siHNK-1 transfection reduced the NFκB activity compared with cells that were transfected with scrambled siRNA, before and after TNFα/IL-1β stimulation. This is the first report indicating that NFκB 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.

KW - Blood-brain/nerve barrier

KW - Endothelial cell

KW - Glycosphingolipid

KW - Human natural killer antigen

KW - NFκB signaling

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