Cyclosporin A blocks induction of tumor necrosis factor-alpha in human B lymphocytes.
The effects of cyclosporin A (CSP) on tumor necrosis factor-alpha (TNF-alpha) RNA levels and protein production in human B cells and a B cell line were studied. The ability of CSP to block induction of RNA was compared to its inhibition of protein production in response to anti-IgM, phorbol ester (PMA) and platelet-activating factor (PAF). PAF is a phospholipid which has recently been found to activate human B cells. CSP blocks PAF-induced TNF-alpha RNA from the Ramos cell line, as well as inhibiting the enhancement of TNF protein production from both freshly isolated and Ramos B cells. CSP also blocks anti-Ig induced TNF-alpha RNA and protein but does not inhibit PMA-induced TNF-alpha. We conclude that B cells, like T cells, have CSP-independent and CSP-dependent signaling pathways and that PAF signaling is dependent upon a CSP-sensitive factor.
Smith
C S
CS
Department of Pediatrics, Baylor College of Medicine.
Ortega
G
G
Parker
L
L
Shearer
W T
WT
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000494:pharmacology; D012313:RNA / Q000032:analysis / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D015850:Interleukin-6; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate