Date Published:
09/2011

Publication Type:
Journal Article

Authors:

Ashutosh
W. Kou
R.L. Cotter
K. Borgmann
L. Wu
R. Persidsky
N. Sakhuja
A. Ghorpade

Secondary:
Biochemical and Biophysical Research Communications

Volume:
412

Pagination:
565-571

Issue:
4

URL:
https://pubmed.ncbi.nlm.nih.gov/

DOI:
10.1016/j.bbrc.2011.07.127

Keywords:
Alzheimer’s disease (AD);Amyloid-β (Aβ);CXCL8;External;Human neuron;Neuroprotection;Tumor necrosis factor-α (TNF-α)

Abstract:
<p>Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-β (Aβ) deposition in senile plaques colocalized with activated microglia and astrocytes. Recent studies suggest that CXCL8 is involved in the AD pathogenesis. The objective of this study was to determine the cellular sources of CXCL8 in the central nervous system during AD pathogenesis, and investigate the effects of CXCL8 on neuronal survival and/or functions. Our results showed significantly higher CXCL8 levels in AD brain tissue lysates as compared to those of age-matched controls. Upon Aβ and/or pro-inflammatory cytokine stimulation, microglia, astrocytes and neurons were all capable of CXCL8 production in vitro. Although CXCL8-alone did not alter neuronal survival, it did inhibit Aβ-induced neuronal apoptosis and increased neuronal brain-derived neurotrophic factor (BDNF) production. We conclude that microglia, astrocytes and neurons, all contribute to the enhanced CXCL8 levels in the CNS upon Aβ and/or pro-inflammatory cytokine stimulation. Further, CXCL8 protects neurons possibly by paracrine or autocrine loop and regulates neuronal functions, therefore, may play a protective role in the AD pathogenesis.</p>