Basic fibroblast growth factor-2 and interleukin-1 β regulate S100 β expression in cultured astrocytes

Abstract

Basic fibroblast growth factor and interleukin-1 β are known to regulate the expression of other trophic factors and to stimulate reactive gliosis in vivo. S100 β is a glial-specific putative neurotrophic factor and has been considered a marker of the reactive status of astrocytes. Therefore, we tested the hypothesis that basic fibroblast growth factor-2 and interleukin-1 β achieve their effects by altering S100 β gene expression in cultured rat astrocytes using an RNase protection assay. Short-term treatment with basic fibroblast growth factor-2 produced a transient decrease in S100 β messenger RNA which was followed by an increase after longer term treatment. In contrast, both short- and long-term treatment with interleukin-1 β suppressed S100 β messenger RNA. We measured levels of S100 β nuclear primary transcript to assess whether alterations in transcriptional rate explain the changes in messenger RNA. Our results indicate that changes in transcription account for changes in steady state levels of messenger RNA since basic fibroblast growth factor-2-induced changes in S100 β primary transcript temporally preceded changes in messenger RNA. We further measured intracellular S100 β protein levels by enzyme-linked immunosorbent assay to determine whether changes in gene expression were translated into parallel changes in protein. Our results clearly demonstrate that basic fibroblast growth factor-2 and interleukin-1 β influence the expression of the S100 β gene, that this regulation appears to occur at the level of transcription, and that alterations in messenger RNA are sometimes, but not always, reflected in changes at the level of protein. These observations suggest that basic fibroblast growth factor-2 may amplify its trophic effects, in part, by influencing the expression of another trophic factor.