MODULATION OF SURFACE TNF EXPRESSION BY HUMAN LEUKEMIC-CELLS ALTERS THEIR SENSITIVITY TO EXOGENOUS TNF

In this study, U937 leukaemic cells underwent apoptotic cell death fol lowing exposure to TNF. Pre-incubation of cells for 48 h with VitD(3) (10(-8) M) induced resistance to TNF, whereas incubation with tau-IFN or GM-CSF increased susceptibility to TNF. Resistance to exogenous TNF (exTNF) following culture with VitD(3) was associated with increased expression of endogenous TNF (enTNF). The TNF inhibitors pentoxifyllin e (PTF) and dichloroisocoumarin (DCI) inhibited TNF synthesis by U937 cells and abrogated the increase in resistance to TNF seen with VitD(3 ). The tau-IFN increased TNF expression, whereas GM-CSF had little eff ect. The data show that the sensitivity of leukaemic cells to exTNF ca n be modulated by cytokines. The protective effect of VitD(3) is media ted in part by directly upregulating enTNF synthesis.