Dopamine induces TNFα and TNF-R1 expression in SH-SY5Y human neuroblastoma cells

Cytotoxic concentrations of dopamine (100-500 mu M DA) induce expression of tumour necrosis factor receptor-1 (TNF-RI) and tumour necrosis factor-alpha (TNF alpha) in SH-SY5Y human neuroblastoma cells. TNF alpha expression is dose-dependent and can also be detected after 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium iodide (MPP+) treatment. The expression of TNF-RI is also dose-dependent, but was not observed in 6-OHDA or MPP+-treatment. Cells not expressing TNF-RI were insensitive to TNFa, whereas those treated with DA showed a further decrease in viability when subsequently treated with TNF alpha Thus, DA treatment confers sensitivity to TNF alpha The decrease of cell viability caused by DA was in part prevented by neutralizing TNF alpha with anti-TNF alpha. As TNF-RI is increased in substantia nigra of Parkinsonian brains, we suggest that nonvesiculated DA might also play a role in inducing TNF-RI expression and predispose the neuron to the action of cytokines released in a microglia-mediated inflammatory response. NeuroReport 18:1725-1728 (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.