Evaluation of human astrocytoma and glioblastoma cell lines for nerve growth factor release.

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.