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.
Hahn
M
M
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Lorez
H
H
Fischer
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology*; D002460:Cell Line; D004357:Drug Synergism; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014746:Vimentin / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D016859:Lipoxygenase Inhibitors; D009414:Nerve Growth Factors; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta; D014746:Vimentin; D003994:Bucladesine; D011493:Protein Kinase C