Differentiation-inducing and cytotoxic effects of tumor necrosis factor and interferon-gamma in myeloblastic ML-1 cells

✍ Scribed by Ruth W. Craig; Heather L. Buchan

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 739 KB
• Volume: 141
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041410108

✦ Synopsis

The effects of the tumor necrosis factor (TNF), and a second pleiotropic cytokine interferon-gamma (IFN), were examined in a line of human myeloblastic leukemia cells (ML-1). By itself, TNF causes ML-1 to differentiate along the monocytic pathway. The cells exhibit an increase in Fc receptors and acquire the morphological characteristics of maturing phenotype. They remain viable and continue to proliferate (at 2 50% of the control growth rate) even with 102-104 unitshl TNF.

IFN alone has similar effects, causing an increase in Fc receptors but little cytotoxicity. In contrast to either cytokine alone, the combination of TNF plus IFN causes a cessation of proliferation and extensive cell death. Cytotoxicity occurs in a synergistic fashion; it requires the simultaneous presence of both cytokines, occurring with concurrent but not sequential exposure. These different responses, differentiation (TNF alone) and cytotoxicity (TNF + IFN), occur with a similar range of doses (-1 02-104 unitshl) and in a similar time frame (beginning on day 2). In other cell types, IFN can augment either the differentiation-inducing or the cytotoxic effect of TNF. In ML-I, the combined application of TNF plus IFN results in a shift from differentiation to cytotoxicity.