INTERFERON-GAMMA-INDUCED DIFFERENTIATION AND APOPTOSIS OF HT29 CELLS - DISSOCIATION OF (GLUCOSYL)CERAMIDE SIGNALING

Recently, (glyco)sphingolipids (SL) like ceramide (Cer) and glucosylce ramide (GlcCer) have been shown to be involved in signaling pathways l eading to differentiation and apoptosis in several cell types, includi ng the colon adenocarcinoma cell line HT29. Intracellular levels of Ce r can be modulated by ligands such as interferon-gamma (IFN gamma). In the present study we show that IFN gamma, depending on its concentrat ion, has both differentiation- and apoptosis-inducing effects on HT29 cells. Since both phenomena have been related to SL-mediated signaling in other cell types, we next examined whether IFN gamma was able to i nduce changes in the SL levels of HT29 cells. Remarkably, no significa nt changes in these levels could be revealed, implying that SL are not involved in IFN gamma-induced differentiation and/or apoptosis of HT2 9 cells. This observation provides evidence for the hypothesis that SL -mediated signaling pathways might be more cell type specific than is generally assumed. (C) 1998 Academic Press.