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.