Dopamine induces TNFalpha and TNF-R1 expression in SH-SY5Y human neuroblastoma cells.
Cytotoxic concentrations of dopamine (100-500 microM DA) induce expression of tumour necrosis factor receptor-1 (TNF-R1) and tumour necrosis factor-alpha (TNFalpha) in SH-SY5Y human neuroblastoma cells. TNFalpha 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 TNFalpha, whereas those treated with DA showed a further decrease in viability when subsequently treated with TNFalpha. Thus, DA treatment confers sensitivity to TNFalpha. The decrease of cell viability caused by DA was in part prevented by neutralizing TNFalpha with anti-TNFalpha. 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.
Gómez-Santos
Cristina
C
Biochemistry Unit, Department of Physiological Sciences II, University of Barcelona - IDIBELL, Barcelona, Spain.
Francisco
Roser
R
Giménez-Xavier
Pol
P
Ambrosio
Santiago
S
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D009498:Neurotoxins; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D016627:Oxidopamine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine