Sulfoglucuronosyl paragloboside is a ligand for T cell adhesion: Regulation of sulfoglucuronosyl paragloboside expression via nuclear factor κB signaling
✍ Scribed by Somsankar Dasgupta; Jeane Silva; Guanghu Wang; Robert K. Yu
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 193 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Inflammatory cytokines such as tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β 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 TNFα stimulation. A thorough screening of the signaling system confirmed that TNFα/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. © 2009 Wiley‐Liss, Inc.