Sulfoglucuronosyl paragloboside is a ligand for T cell adhesion: regulation of sulfoglucuronosyl paragloboside expression via nuclear factor kappaB signaling.
J Neurosci Res
; 87(16): 3591-9, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19533738
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Linfócitos T
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NF-kappa B
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Globosídeos
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article