Tumor necrosis factor-alpha and nerve growth factor synergistically induce iNOS in pheochromocytoma cells

Inducible nitric oxide synthase (iNOS) has been reported in tangle-bearing neurons of patients with Alzheimer's disease (AD), and can be induced by tumor necrosis factor-α (TNFα). High CNS levels of TNFα are associated with neurodegenerative diseases such as AD, where neurons dependent on neurotrophins such as nerve growth factor (NGF) are particularly affected. In this study we determined the effect of TNFα on iNOS in NGF-responsive pheochromocytoma (PC12) cells. We found that while TNFα and NGF alone were unable to induce iNOS, their simultaneous addition resulted in iNOS induction and the release of nitric oxide. Our results suggest their synergistic iNOS induction by TNFα and NGF may occur in selective population of NGF-responsive neurons in the presence of elevated CNS levels of TNFα. (C) 2000 Lippincott Williams and Wilkins.