THE IMMORTALIZED ASTROGLIAL CELL-LINE RC7 IS A NEW MODEL SYSTEM FOR THE STUDY OF NERVE GROWTH-FACTOR (NGF) REGULATION - STIMULATION BY INTERLEUKIN-1-BETA AND TRANSFORMING GROWTH-FACTOR-BETA-1 IS ADDITIVE AND AFFECTED DIFFERENTLY BY DIBUTYRYL-CYCLIC-AMP

Nerve growth factor (NGF) synthesis was studied with an astroglial cell line derived from rat cerebellar astrocytes by transfection with a simian virus 40 T containing retroviral vector. As in primary astrocytes, NGF synthesis/secretion could be stimulated dose-dependently with interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1). We therefore have used this cell line as a model system to analyze putative intracellular signalling pathways underlying the effects of these factors. Protein kinase C inhibitors (calphostin and Ro 31-8830) as well as a lipoxygenase inhibitor (nordihydroguaiaretic acid) did not affect stimulation of NGF synthesis/secretion by IL-1beta or TGF-beta1. However, dibutyryl cyclic AMP partly inhibited the stimulation by TGF-beta1 but did not affect that evoked by IL-1beta. This finding, together with the fact that IL-1beta and TGF-beta1 stimulate NGF production/secretion in an additive manner, indicates that different intracellular signalling pathways are involved in the mediation of IL-1beta and TGF-beta1 induced NGF production/secretion. (C) 1994 Wiley-Liss, Inc.