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.
Dasgupta
Somsankar
S
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
Yanagisawa
Makoto
M
Krishnamurthy
Kannan
K
Liour
Sean S
SS
Yu
Robert K
RK
D000906:Antibodies / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000201:enzymology* / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002461:Cell Line, Transformed; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004357:Drug Synergism; D004660:Encephalitis / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005915:Globosides / Q000276:immunology / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D005915:Globosides; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C051917:sulfate-3-glucuronyl paragloboside; D019041:L-Selectin; D014453:Glucuronosyltransferase