Interleukin-1β mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway

Neural precursor cells (NPCs) have been experimentally used to repair the damaged nervous system either by exogenous transplantation or by endogenous activation. In post-injury inflammation, an array of cytokines including interleukin-lp (IL-1 beta) are released by host as well as invading immune cells and increased markedly. In the present study, we investigated the effects of IL-1 beta on the survival, proliferation, differentiation and migration of NPCs as well as underlying intracellular signaling pathways. NPCs derived from the E16 rat brain were expanded in neurospheres that were found to express IL-1 beta, ILRII and IL-IRII, but not IL-I alpha and IL-Ira. IL-1 beta inhibited the proliferation of NPCs in a dose-dependent manner, an effect that can be reversed by IL-Ira, an antagonist for IL-1 receptor. This inhibitory effect of IL-1 P on NPCs proliferation resulted in part from its effect on increased apoptosis of NPCs. Moreover, IL-Ira did not affect NPCs lineage fate but rather inhibited GFAP expression in differentiated astrocytes. We also found that IL-1ra had no effect on the transmigration of NPCs in vitro. Finally, we showed that the effect of IL-I beta on NPCs proliferation and differentiation appeared to be mediated by SAPK/JNK, but not ERK, P38MAPK nor NF-kappa B pathways. These findings collectively suggest that the inflammatory environment following CNS injuries may influence the ability of NPCs to repair the damage. (c) 2007 Elsevier Inc. All rights reserved.