Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

Interleukin-1 (IL-1) is a critical neuroinflammatory mediator in the central nervous system (CNS). In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1 beta) is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1 beta stimulation. The three astrocyte cell lines responded to IL-1 beta stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1 beta stimulation. The brain endothelial cells showed strongest response to IL-1 beta by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be - mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-kappa B pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.