Astrocytes stimulate interleukin-17 and interferon-gamma production in vitro

Abstract

Astrocytes play important roles in the complex and as yet not very well understood net of interactions among resident and infiltrating cells during central nervous system (CNS) inflammation. In such an intricate network, cytokines represent an essential means for intercellular communication, and astrocytes are able to affect their generation and/or release. Among various cytokines produced by infiltrating cells, interferon (IFN)-gamma and interleukin (IL)-17 are the focus of this research, because they are pivotal cytokines of helper T-cell type 1 (Th1) and helper T-cell type 17 (Th17), respectively. Importantly, both Th1 and Th17 cells, as well as their cytokines, have been shown to be of importance for the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of a prototypical CNS disease with inflammatory pathogenesis, multiple sclerosis. Therefore, the influence of astrocytes on the generation of IFN-gamma and IL-17 in concanavalin A- and myelin basic protein-stimulated lymph node cells of healthy rats and rats with developing EAE, respectively, was investigated in vitro. Astrocytes up-regulated IL-17 and IFN-gamma gene expression and protein synthesis in T cells, which coincided with astrocytes' ability to express IL-23 subunit p19 and common IL-12/IL-23 subunit p40 but not IL-12 subunit p35 in the cocultivations. These results suggest one more way in which astrocytes could contribute to the complex interactions during CNS inflammation. (C) 2007 Wiley-Liss, Inc.