TY - JOUR
T1 - CXCL8 protects human neurons from amyloid-β-induced neurotoxicity
T2 - Relevance to Alzheimer's disease
AU - Ashutosh,
AU - Kou, Wei
AU - Cotter, Robin
AU - Borgmann, Kathleen
AU - Wu, Li
AU - Persidsky, Raisa
AU - Sakhuja, Namita
AU - Ghorpade, Anuja
N1 - Funding Information:
This study was supported by grants from the NINDS, RO1 NS48837, NIMH, MH087345 to A. Ghorpade and additional support from J.E.S. Edwards Foundation, Fort Worth, TX. The project entitled “Laboratory of Developmental Biology” was supported by NIH 5R24HD0008836 from NICHD. Also supported by NIMH and NINDS funding to: Manhattan HIV Brain Bank, U01MH083501, R24MH59724; Texas NeuroAIDS Research Center U01MH083507, R24 NS45491; National Neurological AIDS Bank 5U01MH083500, NS38841; California NeuroAIDS Tissue Network U01MH083506, R24MH59745; Statistics and Data Coordinating Center U01MH083545, N01MH32002. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NICHD, NNTC or NIH. The authors thank the families of donors to the CNND Brain Bank, the Laboratory of Developmental Biology and the NNTC for their contribution to this research.
PY - 2011/9/9
Y1 - 2011/9/9
N2 - 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.
AB - 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.
KW - Alzheimer's disease (AD)
KW - Amyloid-β (Aβ)
KW - CXCL8
KW - Human neuron
KW - Neuroprotection
KW - Tumor necrosis factor-α (TNF-α)
UR - http://www.scopus.com/inward/record.url?scp=80052621321&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2011.07.127
DO - 10.1016/j.bbrc.2011.07.127
M3 - Article
C2 - 21840299
AN - SCOPUS:80052621321
SN - 0006-291X
VL - 412
SP - 565
EP - 571
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -