Tumor necrosis factor-alpha up-regulates glucuronosyltransferase gene expression in human brain endothelial cells and promotes T-cell adhesion.

Stimulation of human brain microvascular endothelial cells (SV-HCECs) with tumor necrosis factor-alpha (TNF-alpha) up-regulates sulfoglucuronosyl paragloboside (SGPG) synthesis in a dose- and time-dependent manner. After TNF-alpha exposure at a concentration of 50 ng/ml for 24 hr, we observed a seven- to tenfold elevation of SGPG concentration. Interleukin-1beta (IL-1beta) at a concentration of 10 ng/ml and the combined doses of TNF-alpha and IL-1beta were less effective than TNF-alpha alone. TNF-alpha also stimulated T-cell (Jurkat) adhesion with SV-HCECs via SGPG-L-selectin recognition: this was determined by double-label immunofluorescent staining with SGPG and L-selectin antibodies. The number of T cells bound to SV-HCECs after different cytokine stimulations was proportional to the SGPG concentration, and the cell attachment was inhibited by anti-SGPG and anti-L-selectin antibodies, respectively. Our data unequivocally establish that inflammatory cytokines, particularly TNF-alpha, stimulate the glucuronosyltransferse, GlcAT-P, and GlcAT-S, gene expression in brain endothelial cells and promote T-cell adhesion via SGPG-L-selectin recognition, a preliminary step for onset of neuroinflammation.