Soluble amyloid β-peptide and myelin basic protein strongly stimulate, alone and in synergism with combined proinflammatory cytokines, the expression of functional nitric oxide synthase-2 in normal adult human astrocytes

  • Authors:
    • Anna Chiarini
    • Ilaria Dal Pra
    • Lia Menapace
    • Raffaella Pacchiana
    • James F. Whitfield
    • Ubaldo Armato
  • View Affiliations

  • Published online on: November 1, 2005     https://doi.org/10.3892/ijmm.16.5.801
  • Pages: 801-807
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Abstract

The accumulation of amyloid β (Aβ)-peptides and their collection in fibrillar plaques in the human brain are believed to be responsible for Alzheimer's disease. The major neuron killers in the Alzheimer brain include proinflammatory cytokines and NO made by NOS-2 (inducible nitric oxide synthase-2). We have determined the effect of a soluble Aβ peptide, Aβ(1-40), on the expression of NOS-2 in astrocytes using a novel model system consisting of pure cultures of cells from adult human brains that, after the first three passages in vitro, become stably locked into the normal astrocytic phenotype like their counterparts in the adult human brain. Aβ(1-40) alone stimulated quiescent astrocytes to start expressing functional NOS-2 and dumping NO into the culture medium during the next 4 days. But adding three of the proinflammatory cytokines commonly produced in the Alzheimer brain - IFN-γ, IL-1β, and TNF-α - along with Aβ(1-40) more than trebled NOS-2 expression and doubled NO production. In view of the possibility of myelin breakdown in the Alzheimer brain, we also tested the capability of myelin basic protein (MBP) to stimulate NO production using human astrocytes. We found that MBP mimicked the ability of Aβ(1-40) to induce cells to release NO and adding the cytokine triad along with MBP more than doubled NO production and release. Thus, it appears that Aβ peptides and MBP can join forces with proinflammatory cytokines to enhance the NO-mediated killing of neurons in the Alzheimer brain.

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November 2005
Volume 16 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chiarini A, Dal Pra I, Menapace L, Pacchiana R, Whitfield JF and Armato U: Soluble amyloid β-peptide and myelin basic protein strongly stimulate, alone and in synergism with combined proinflammatory cytokines, the expression of functional nitric oxide synthase-2 in normal adult human astrocytes. Int J Mol Med 16: 801-807, 2005
APA
Chiarini, A., Dal Pra, I., Menapace, L., Pacchiana, R., Whitfield, J.F., & Armato, U. (2005). Soluble amyloid β-peptide and myelin basic protein strongly stimulate, alone and in synergism with combined proinflammatory cytokines, the expression of functional nitric oxide synthase-2 in normal adult human astrocytes. International Journal of Molecular Medicine, 16, 801-807. https://doi.org/10.3892/ijmm.16.5.801
MLA
Chiarini, A., Dal Pra, I., Menapace, L., Pacchiana, R., Whitfield, J. F., Armato, U."Soluble amyloid β-peptide and myelin basic protein strongly stimulate, alone and in synergism with combined proinflammatory cytokines, the expression of functional nitric oxide synthase-2 in normal adult human astrocytes". International Journal of Molecular Medicine 16.5 (2005): 801-807.
Chicago
Chiarini, A., Dal Pra, I., Menapace, L., Pacchiana, R., Whitfield, J. F., Armato, U."Soluble amyloid β-peptide and myelin basic protein strongly stimulate, alone and in synergism with combined proinflammatory cytokines, the expression of functional nitric oxide synthase-2 in normal adult human astrocytes". International Journal of Molecular Medicine 16, no. 5 (2005): 801-807. https://doi.org/10.3892/ijmm.16.5.801