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-1 beta (IL-1 beta) and transforming growth factor-beta 1 (TGF-beta 1). 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-1 beta or TGF-beta 1. However, dibutyryl cyclic AMP partly inhibited the stimulation by TGF-beta 1 but did not affect that evoked by IL-1 beta. This finding, together with the fact that IL-1 beta and TGF-beta 1 stimulate NGF production/secretion in an additive manner, indicates that different intracellular signalling pathways are involved in the mediation of IL-1 beta and TGF-beta 1 induced NGF production/secretion.