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 language | English (US) |
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Pages (from-to) | 3591-3599 |
Number of pages | 9 |
Journal | Journal of Neuroscience Research |
Volume | 87 |
Issue number | 16 |
DOIs | |
State | Published - Dec 2009 |
Keywords
- Blood-brain/nerve barrier
- Endothelial cell
- Glycosphingolipid
- Human natural killer antigen
- NFκB signaling
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience