title: Evaluation of human astrocytoma and glioblastoma cell lines for nerve growth factor release.
abstract: Nerve growth factor (NGF) prevents degeneration of cholinergic neurons in the central nervous system (CNS), and has potential as a therapeutic treatment for Alzheimer's disease. The inability of NGF to cross the blood-brain barrier has prompted pharmacological approaches investigating peripherally administered compounds that stimulate release of endogenous NGF. This study describes the NGF-releasing properties of six human astrocytoma and glioblastoma cell lines (SW 1088, SW 1783 and CRL 1718 astrocytomas, and U-138, U-373, and T98G glioblastomas). Using a highly specific two-site ELISA for human NGF, basal NGF release could be detected in all cell lines, with the lowest level in the T98G line (approximately 80 pg NGF/ml). Cell lines tested with a variety of compounds for 24 h in serum-free media demonstrated stimulation of NGF release by distinct mechanisms. NGF levels were markedly elevated (up to 8-fold above vehicle-treated cells) when stimulated with the cytokine interleukin-1 beta (IL-1 beta). Phorbol ester stimulated NGF release 4-fold. Clenbuterol, 4-methyl catechol, and propentofylline had little activity, while 6-(4-hydroxybutyl)-2,3,5,-trimethyl-1,4,benzoquinone (TMQ), dexamethasone and 1,25-dihydroxyvitamin D3 elevated NGF levels 3-fold. These data indicate differences in the ability of human astrocytoma and glioblastoma cells to release NGF when stimulated with mechanistically distinct compounds.
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, R2-101 Neurobiology Unit Roche Bioscience, Palo Alto, CA 94304, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Emmett
authors.forename: P A
authors.initials: PA
authors.lastname: McNeeley
authors.forename: R M
authors.initials: RM
authors.lastname: Johnson
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001254:Astrocytoma / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008940:Mitotic Index; D009414:Nerve Growth Factors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000318:Adrenergic beta-Agonists; D007375:Interleukin-1; D009414:Nerve Growth Factors; D005576:Colforsin; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate