DEXAMETHASONE-DEPENDENT MODULATION OF HUMAN LYMPHOBLASTOID B-CELL LINE THROUGH SPHINGOSINE PRODUCTION

The relationship between dexamethasone-dependent changes in intracellu lar sphingosine levels, energy and phospholipid metabolism have been i nvestigated by P-31-NMR spectroscopy and high-performance liquid chrom atography. The cellular functions have been evaluated by cellular grow th and immunoglobulin M secretion (IgM). Significant increases in intr acellular phosphorylcholine (PCho), extracellular choline (Cho), and e ndogenous sphingosine levels were observed only at 30 min incubation w ith dexamethasone. These results confirmed a sphingosine-dependent hyd rolysis of choline-linked phospholipids (Miccheli, A., Ricciolini, R., Piccolella, E., Delfini, M. and Conti, F. (1991) Biochim. Biophys. Ac ta 1093, 29-35). Furthermore, no significant variations were evidenced at hours 1, 2, 6 and 18 of incubation. Dexamethasone causes an inhibi tion of cellular growth and IgM secretion as well as the sphingosine t reatment. The results suggest that the effect of dexamethasone may be mediated by endogenous sphingosine production in Epstein-Barr virus tr ansformed B lymphocytes.