Cytokines regulate expression of the type 1 interleukin-1 receptor in rat hippocampal neurons and glia

Interleukin-1 beta is a key mediator of inflammation and stress in the central nervous system (CNS). This cytokine induces CNS glial cells to produce numerous additional cytokines and growth factors under inflammatory conditions. We have investigated regulation of the signal transducing type 1 interleukin-l receptor (IL-IRI) in the CNS, In vivo, IL-1R1 was not detected in glial cells under basal conditions but was strongly induced after a stab lesion. Cultured astrocytes were used to identify specific signals that regulate expression of the receptor. IL-1R1 mRNA and protein were induced by inflammatory stimuli including tumor necrosis factor (TNF alpha) and IL-1 beta itself. Although expression of the receptor was not detected in glia under basal conditions in vivo, pyramidal neurons in the hippocampus expressed the IL-1 receptor in the normal, unlesioned brain. Cultured embryonic hippocampal neurons were used to investigate specific stimuli that regulate IL-1R1 in neurons. As in astrocytes, IL-1 and TNF alpha induced expression of IL-1R1. The expression of IL-1R1 in hippocampal neurons suggests a possible role for IL-l in regulating neuronal function, and indicates that these neurons may be directly influenced by cytokines. (C) 2001 Academic Press.