Interleukin-1β stimulates mitogen-activated protein kinase in U373 astrocytoma cells without the production of lipid second messengers

IL-1β is one of the cytokines known to affect astroglial cells in normal brain development, brain injury and neurodegenerative diseases. IL- 1β causes astrocytes to become more reactive, alter the expression and release of molecules and in some cases of proliferate. We have investigated the mitogenic effect and signal transduction pathway induced by IL-1β in U373 cells, a human astrocytoma cell-line. Recombinant human IL-1β induced mitogenesis of U373 cells in a dose-dependent fashion as assessed by tritiated thymidine incorporation. The following signal transduction mechanisms, reported to be induced in other systems by IL-1β, were investigated in U373 cells: (1) activation of phosphatidylcholine-specific phospholipase C as assayed by incorporation of tritiated choline into cellular phospholipids, (2) production of diacylglycerol, a lipid second messenger, (3) activation of sphingomyelinase, and (4) activation of mitogen- activated protein kinase (MAPK). Of these, IL-1β activated only MAPK. In cultured rat astrocytes, IL-1β caused activation of MAPK without inducing proliferation.