Research report
Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1

https://doi.org/10.1016/0169-328X(92)90202-MGet rights and content

Abstract

The origin of β-amyloid deposited in senile plaques in Alzheimer's disease (AD) is not known. We compared the expression of protein precursor of β-amyloid (APP) in the cell types involved in plaque formation. The levels of APP mRNA were determined in primary rat neurons and glial cells in culture, human endothelial cells and in a murine brain-derived endothelial cell line. Northern blot analysis was performed using an APP cDNA probe to detect the general APP sequence and an oligonucleotide (40 mer) complementary to the sequence of the Kunitz protease inhibitor (APP-KPI). The APP mRNA transcripts were abundant in all three cell types. The highest level of APP, normalized to β-actin mRNA content, was expressed in neurons, followed by glial cells, where the APP expression was similar (94%) while in endothelial cells was lower (53%). The proportion between APP-KPI mRNA and total APP mRNA was high in endothelial, intermediate in glial and low in neuronal cells. We compared the effects of exposure to interleukin-1 (IL-1), a cytokine involved in several biological processes and elevated in AD, on APP mRNA expression in neuronal, glial and endothelial cells. In human endothelial and in brain-derived murine endothelial cells we observed a similar increase (50%) of total APP-mRNA or APP-KPI mRNA after treatment with human recombinant IL-1β. In neuronal cells, IL-1 (200 ng/ml) substantially increased APP mRNA (175%), detected with both probes. In glial cells, the expression of APP mRNA did not appear to be altered by IL-1 (50–400 ng/ml). The results suggest a role of IL-1 in the neuronal mechanism related to β-amyloid protein deposition in AD

References (62)

  • R.L. Neve et al.

    The neuronal growth associated protein GAP-43 (B-50, F1): neuronal specificity, developmental regulation and regional distribution of the huma and rat mRNAs

    Mol. Brain Res.

    (1987)
  • R.L. Neve et al.

    Expression of the Alzheimer's amyloid precursor gene transcripts in the human brain

    Neuron

    (1988)
  • R.L. Neve et al.

    The Alzheimer's amyloid precursor-related transcript lacking the β/A4 sequence is specifically increased in Alzheimer's disease brain

    Neuron

    (1990)
  • G.W. Roberts et al.

    βA4 amyloid protein deposition in brain after head trauma

    Lancet

    (1991)
  • D.J. Selkoe

    The molecular pathology of Alzheimer's disease

    Neuron

    (1991)
  • R. Siman et al.

    Expression of β-amyloid precursor protein in reactive astrocytes following neuronal damage

    Neuron

    (1989)
  • C.J. Smith et al.

    Nerve growth factor-induced neuronal differentiation is accompanied by differential splicing of β-amyloid precursor mRNAs in the PC 12 cell line

    Mol. Brain Res.

    (1991)
  • S. Tanaka et al.

    Three types of amyloid protein precursor mRNA in human brain: their differential expression in Alzheimer's disease

    Biochem. Biophys. Res. Commun.

    (1988)
  • M.P. Vitek et al.

    Absence of mutation in the β-amyloid cDNAs cloned from the brains of three patients with sporadic Alzheimer's disease

    Mol. Brain Res.

    (1988)
  • R.L. Williams et al.

    Endothelioma cells expressing the polyoma middle T oncogene induce hemangiomas by host cell recruitment

    Cell

    (1989)
  • S. Bahmanyer et al.

    Localization of amyloid β protein messenger RNA in brains from patients with Alzheimer's disease

    Science

    (1987)
  • B. Barbieri et al.

    Evidence that vascular endothelial cells can induce tha retraction of fibrin clots

  • C. Bendotti et al.

    Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid and lesioned mice

  • C. Bendotti et al.

    Distribution of GAP-43 mRNA in the brain stem of adult rats as evidenced by in situ hybridization: localization within monoaminergic neurons

    J. Neurosci.

    (1991)
  • F. Berkenbosch et al.

    The Alzheimer's amyloid precursor protein is produced by type I astrocytes in primary cultures of rat neuroglia

    J. Neurosci. Res.

    (1990)
  • F. Bussolino et al.

    Murine endothelioma cell lines transformed by polyoma middle T oncogene as target for and producers of cytokines

    J. Immunol.

    (1991)
  • J.P. Card et al.

    Immunocytochemical localization of the precursor protein for β-amyloid in the rat central nervous system

    Neuron

    (1987)
  • M. Carman-Krzan et al.

    Regulation by interleukin 1 of nerve growth factor secretion and nerve growth factor mRNA expression in rat primary astroglial cultures

    J. Neurochem.

    (1991)
  • P. Chomczynsky et al.

    Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction

    Anal. Biochem.

    (1987)
  • P.E. Danielson et al.

    p1B15: cDNA clone of the rat mRNA encoding cyclophilin

    DNA

    (1988)
  • F. De Sauvage et al.

    A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein

    Science

    (1989)
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