Modulation of surface TNF expression by human leukaemic cells alters their sensitivity to exogenous TNF.
In this study, U937 leukaemic cells underwent apoptotic cell death following 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 pentoxifylline(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 effect. The data show that the sensitivity of leukaemic cells to exTNF can be modulated by cytokines. The protective effect of VitD(3) is mediated in part by directly upregulating enTNF synthesis.
Wu
Y L
YL
Department of Haematology, The London Hospital Medical College, UK.
Jiang
X R
XR
Allen
P D
PD
Jia
L
L
Dronfield
D M
DM
Newland
A C
AC
Kelsey
S M
SM
D000470:Alkaloids / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D019311:Staurosporine; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000494:pharmacology*
D000470:Alkaloids; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019311:Staurosporine