BASIC FIBROBLAST GROWTH-FACTOR-II AND INTERLEUKIN-1-BETA REGULATE S100-BETA EXPRESSION IN CULTURED ASTROCYTES

Basic fibroblast growth factor and interleukin-1 beta are known to reg ulate the expression of other trophic factors and to stimulate reactiv e gliosis in vivo. S100 beta is a glial-specific putative neurotrophic factor and has been considered a marker of the reactive status of ast rocytes. Therefore, we tested the hypothesis that basic fibroblast gro wth factor-2 and interleukin-1 beta achieve their effects by altering S100 beta gene expression in cultured rat astrocytes using an RNase pr otection assay. Short-term treatment with basic fibroblast growth fact or-2 produced a transient decrease in S100 beta messenger RNA which wa s followed by an increase after longer term treatment. In contrast, bo th short- and long-term treatment with interleukin-1 beta suppressed S 100 beta messenger RNA. We measured levels of S100 beta nuclear primar y transcript to assess whether alterations in transcriptional rate exp lain the changes in messenger RNA. Our results indicate that changes i n transcription account for changes in steady stale levels of messenge r RNA since basic fibroblast growth factor-2-induced changes in S100 b eta primary transcript temporally preceded changes in messenger RNA. W e further measured intracellular S100 beta protein levels by enzyme-li nked immunosorbent assay to determine whether changes in gene expressi on were translated into parallel changes in protein. Our results clear ly demonstrate that basic fibroblast growth factor-2 and interleukin-1 beta influence the expression of the S100 beta gene, that this regula tion appears to occur at the level of transcription, and that alterati ons in messenger RNA are sometimes, but not always, reflected in chang es at the level of protein. These observations suggest that basic fibr oblast growth factor-2 may amplify its trophic effects, in part, by in fluencing the expression of another trophic factor. (C) 1997 IBRO. Pub lished by Elsevier Science Ltd.