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

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Cytotoxic concentrations of dopamine (100–500 μM DA) induce expression of tumour necrosis factor receptor-1 (TNF-R1) and tumour necrosis factor-α (TNFα) in SH-SY5Y human neuroblastoma cells. TNFα 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-R1 is also dose-dependent, but was not observed in 6-OHDA or MPP+-treatment. Cells not expressing TNF-R1 were insensitive to TNFα, whereas those treated with DA showed a further decrease in viability when subsequently treated with TNFα. Thus, DA treatment confers sensitivity to TNFα. The decrease of cell viability caused by DA was in part prevented by neutralizing TNFα with anti-TNFα. As TNF-R1 is increased in substantia nigra of Parkinsonian brains, we suggest that nonvesiculated DA might also play a role in inducing TNF-R1 expression and predispose the neuron to the action of cytokines released in a microglia-mediated inflammatory response.

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